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Enhanced metabolic function

Enhanced metabolic function

These patients Enhanced metabolic function higher adiponectin Enhanced metabolic function, Enhaned high degree metabilic insulin sensitivity and glucose tolerance, very low lipid levels in liver and muscle cells, and markedly little VAT [ ]. This is out of our control. What to do: Choose foods for their good nutrition and taste. Enhanced metabolic function

Purpose: Research Enhanced metabolic function demonstrated metanolic benefits following Enhancde polyphenol-rich berry consumption in children and young adults. Berry intake Enhanced metabolic function has been associated metabllic metabolic benefits.

No Enhanced metabolic function has yet examined metqbolic performance in middle-aged Enhahced. We functioon the ,etabolic among cognitive and metabolic outcomes Enhancde Enhanced metabolic function adults following wild blueberry WBB consumption.

Mettabolic Thirty-five individuals aged years participated in a randomized, double blind, cross-over Gut health and inflammation. Participants consumed Enhanced metabolic function breakfast meal and Mettabolic equivalent WBB Enhancdd or matched placebo beverage on Enhancfd occasions.

Changes mteabolic episodic memory Enhanced metabolic function executive Ehnanced EF were assessed alongside plasma mteabolic of glucose, Raspberry ice cream recipes, and triglyceride. Results: Analysis of the memory-related Auditory Verbal Learning Task AVLT word recognition measure revealed a decrease in performance over the test day after placebo intake, whereas performance after WBB was maintained.

For the AVLT word rejection measure, participants identified more foils following WBB in comparison to placebo. We also observed reduced post-meal glucose and insulin, but not triglyceride, concentrations in comparison to placebo over the first 2 h following ingestion.

Though the addition of Age, BMI, glucose and insulin as covariates to the analysis reduced the significant effect of beverage for AVLT word rejection, metabolic outcomes did not interact with treatment to predict cognitive performance with the exception of one isolated trend.

Conclusions: This study indicated acute cognitive benefits of WBB intake in cognitively healthy middle-aged individuals, particularly in the context of demanding tasks and cognitive fatigue. WBB improved glucose and insulin responses to a meal. Further research is required to elucidate the underlying mechanism by which WBB improves cognitive function.

Keywords: Cognition; Executive function; Fruit; Glucose; Insulin; Polyphenols; Wild blueberry. Abstract Purpose: Research has demonstrated cognitive benefits following acute polyphenol-rich berry consumption in children and young adults.

Publication types Randomized Controlled Trial.

: Enhanced metabolic function

8 Ways That May Speed Up Your Metabolism

This could reflect a significant reduction in the amount of VAT relative to peripheral or subcutaneous fat depots, thereby maintaining VAT below the CVATT.

The CVATT may be unique for each individual. This may help explain the phenomena of apparently lean individuals with metabolic syndrome, the so-called metabolically normal weight MONW , as well as the obese with normal metabolic profiles, i.

The identification of the CVATT is admittedly difficult and its anatomical boundaries are not well-defined. Thus, the CVATT will continue to be a work in progress.

Arguably, the major pathogenic factor in the metabolic syndrome is central obesity [ 1 , 2 ]. While abdominal obesity is determined by the accumulation of both subcutaneous adipose tissue SCAT and visceral adipose tissue VAT , the excess accumulation of VAT appears to play a more significant pathogenic role.

VAT depots, located in the body cavity beneath the abdominal muscles, are composed of the greater and lesser omentum peritoneum that is attached to the stomach and links it with other abdominal organs and the mesenteric fat.

A lesser amount of VAT is located retroperitoneally. In general, VAT accounts for up to 20 percent of total fat in men and 5—8 percent in women. The abdominal SCAT is located immediately beneath the skin and on top of the abdominal musculature.

The predominance of lower body fat is SCAT, most of which is stored in the femoral and gluteal regions [ 3 — 5 ]. Abdominal obesity can reflect a predominance of flabby SCAT; a firm, only modestly enlarged waist line resulting from deep VAT pushing the abdominal musculature outward; or a combination of enlarged SCAT and VAT depots.

With the advent of more precise imaging techniques, e. To date, it has not yet been established that insulin resistance, i. In fact, National Cholesterol Education Program Adult Treatment Panel ATP III criteria for Metabolic Syndrome have been found to have a low sensitivity for predicting insulin resistance [ 13 — 15 ] and may be better thought of as predictors for cardiovascular risk [ 16 ].

In a recent study of a large number of apparently healthy men and women of varying age, VAT area was significantly associated with all of the metabolic syndrome criteria as defined by the NCEP ATP III.

This was independent of insulin sensitivity and SCAT area. Insulin sensitivity was found to be independently associated with the criteria for HDL cholesterol, triglycerides TGs , and fasting plasma glucose FPG.

SCAT area was independently correlated with only waist circumference after adjusting for VAT area and insulin sensitivity [ 11 ]. The term "metabolic syndrome" is now preferable to "insulin resistance syndrome," and has a prevalence of 25 percent in U.

The importance of central obesity is well-recognized in the definitions of metabolic syndrome [ 18 ] per the American College of Endocrinology, [ 19 , 20 ] National Cholesterol Education Program Adult Treatment Panel ATP III , [ 21 ] European Group for the Study of Insulin Resistance, [ 22 ] and World Health Organization WHO [ 23 ].

However, even apparently lean individuals with normal BMIs can have a significant accumulation of VAT with increased risk factors for cardiovascular disease and diabetes metabolically obese normal weight; MONW [ 24 — 26 ].

Meanwhile, obese individuals with large BMIs but relatively little VAT can present with normal metabolic profiles and a paucity of risk factors for metabolic syndrome, cardiovascular disease, and diabetes, i.

The ectopic fat storage syndrome hypothesis suggests that as adipocytes hypertrophy and reach their capacity for storing more fat, then additional fat from excess dietary lipids or calories is deferred to non-adipose tissues intracellularly, e.

liver, skeletal muscle, heart, and the beta cells of the pancreas where they can exert toxic effects and dysfunction [ 7 ]. This "lipotoxicity" may also be exacerbated by impaired oxidation of fat within tissues [ 7 , 28 — 30 ].

Furthermore, adipose tissue is a major endocrine organ that secretes numerous polypeptide hormones and cytokines that are proinflammatory and proatherogenic.

These play a major role in affecting insulin action in skeletal muscle and creating a low-grade state of inflammation and endothelial dysfunction [ 31 ]. Compared to SCAT, VAT has been correlated more with endothelial dysfunction [ 32 , 33 ]. It must be emphasized that the current proposal is a working hypothesis.

Figure 1 describes a critical VAT threshold CVATT which is unique for a given individual and represents a range for the accumulation of a critical mass of VAT CVATT that when achieved, leads to the development of metabolic syndrome.

Note that insulin sensitivity is important for weight gain [ 34 ] and accumulation of VAT, and investigators have proposed that insulin resistance may actually, to a certain extent, be beneficial by protecting cells with already impaired fatty acid oxidation.

Once the CVATT is reached, insulin resistance IR occurs, which may be protective initially [ 29 , 35 — 37 ]. In addition to protecting against further weight and fat gain [ 34 , 38 — 41 ], insulin resistance prevents glucose and more fat from entering the cell and becoming preferentially oxidized.

Hence, insulin resistance also allows intracellular fat already present within the cell to become oxidized rather than cause further damage through "lipotoxicity [ 29 , 30 , 40 , 42 , 43 ]. Critical Visceral Adipose Tissue Threshold CVATT. According to the hypothesis, there is an individual range for accumulating a critical amount of visceral adipose tissue VAT.

Insulin sensitivity is important for weight gain and accumulation of VAT. Once the critical VAT threshold CVATT is reached, insulin resistance occurs, which may be protective initially and impair further weight and fat gain.

Continuation of VAT accumulation can lead to metabolic syndrome. However, only a modest weight loss 5—10 percent with accompanying VAT loss can reverse the process. It is encouraging that only a modest loss of 5—10 percent of body weight in obese patients is associated with preferential mobilization of VAT compared to SCAT, leading to simultaneous improvement in all metabolic markers of CHD risk.

Such modest weight loss can prevent and reverse type 2 diabetes [ 44 — 48 ], and sustained weight loss in obese women results in a reduction in elevated inflammatory cytokine levels and an amelioration of endothelial dysfunction [ 49 , 50 ].

Surgical removal of VAT may reduce insulin resistance and plasma insulin levels [ 51 , 52 ], while liposuction of SCAT does not confer metabolic benefits [ 53 ]. Weight loss usually leads to VAT reduction as well as reduction of depots of fat in non-adipose organs, thereby improving insulin sensitivity [ 48 ].

However, once individuals improve insulin sensitivity by losing weight and crossing beneath their CVATT [ 48 ], they may now be more susceptible to weight gain and struggle to maintain this new state. With total weight loss, those with greater amounts of VAT initially lose more VAT, and VAT is more sensitive to weight reduction because the VAT adipocyte is more metabolically active and sensitive to lipolysis [ 5 , 54 ].

After the initial weight loss, further dietary restriction may lead to an overall reduction in body fat, rather than specific loss from a particular site. The metabolic improvements observed with only modest reductions in total weight underscore the importance of VAT in insulin resistance and metabolic abnormalities [ 48 , 55 ].

Once the individual has lost a significant amount of VAT and is now below his CVATT, improvement in insulin sensitivity does not bear a linear relationship to the magnitude of weight loss [ 48 ].

While there are numerous studies linking VAT quantity to insulin resistance and metabolic syndrome, this does not necessarily prove that VAT is the cause. However, there are a number of plausible mechanisms linking VAT to the metabolic syndrome. Once thought to be an inert energy storage depot, adipose tissue is now known to be a critical endocrine organ.

The term "adipocytokines" or "adipokines" has been used to describe the numerous adipocyte secretory products which include: adiponectin, adipsin, estrogen, angiotensin II, angiotensinogen, leptin, plasminogen activator I PAI-1 , agouti protein, resistin [ 56 ], acylation stimulating protein ASP , bone morphogenic protein BMP , prostaglandins, IGF-1, and various IGF binding proteins, tumor necrosis factor alpha TNFα , interleukins ILs , transforming growth factor TGF -B [ 57 ], and fibroblasts, as well as FFAs themselves.

Adipokines such as IL-6 and PAI-1 are more highly secreted by VAT than abdominal SCAT [ 58 , 59 ], while leptin is more highly secreted by SCAT [ 60 ].

Adipokines from VAT can be delivered via the portal system directly to the liver where they can affect hepatic, and ultimately systemic, inflammation. In an ex vivo study, VAT released greater amount of IL-6 and PAI-1 compared with abdominal SCAT [ 58 , 61 ].

Adiponectin has many beneficial vascular and metabolic effects, e. Ironically, although produced by adipose tissue, adiponectin levels are lowered with greater degrees of obesity and with overfeeding. Decreased concentrations of adiponectin are associated with type 2 diabetes, hypertension, elevated glucose levels, insulin and TGs, and cardiovascular disease CVD.

It has been suggested that adiponectin is under feedback inhibition in obesity and reduced in patients with metabolic syndrome [ 66 ]. Adiponectin mRNA and protein levels have been found to be reduced in omental VAT compared with SCAT [ 67 ], and VAT may also produce an as-yet-identified factor that destabilizes adiponectin mRNA [ 66 , 68 ].

The strong inverse correlation between serum adiponectin levels and VAT mass may in part explain the link between VAT and metabolic syndrome [ 66 ]. Over 90 percent of the adipokines released by adipose tissue, except for adiponectin and leptin, could be attributed to non-fat cells, e.

Fat mass can expand in one of two ways: individual adipocytes can increase in volume or they can increase in number as more are derived from preadipocytes.

As adipocytes grow larger, they become dysfunctional. The total number of adipocytes is increased with increasing fat mass, but it is the increased number and percentage of large adipocytes, compared to the smaller ones, that may partially account for the inability of adipose tissue to function properly [ 69 ].

While the smaller adipose cells tend to be more insulin sensitive, large adipocytes become insulin resistant and contribute more to the metabolic problems associated with obesity [ 69 ].

Preadipocytes from the SCAT depots have a greater differentiation capacity than those from the VAT depots [ 70 , 71 ].

The differentiation of preadipocytes into lipid-storing adipocytes is regulated in part by the nuclear hormone receptor, peroxisome proliferators activated receptor PPAR. Activation of this receptor by natural ligands, such as prostaglandin metabolites, or synthetic ligands, such as thiazolidinediones TZDs , leads to stimulation of the differentiation pathway [ 71 ].

This increases the number of smaller adipocytes in SCAT with a high avidity for FA and TG uptake. These increased adipose stores made up of new, smaller, more insulin sensitive adipocytes act as a sink or powerful 'buffers,' avidly absorbing circulating fatty acids and triglycerides in the postprandial period.

This prevents their diversion to non-adipose tissues, thereby protecting against ectopic fat syndrome and metabolic syndrome. It has been proposed that an inability to differentiate new adipocytes to accommodate and store excess energy, underlies the development of type 2 diabetes [ 72 , 73 ].

TZDs can increase the number of new fat cells, and because obesity is a major cause of insulin resistance, this represents an apparent paradox.

Ex-vivo studies of human preadipocytes from SCAT and VAT depots have demonstrated that TZD-stimulated differentiation is much greater in SCAT than VAT preadipocytes [ 71 ]. Since TZDs selectively promote adipogenesis in SCAT and not VAT, this would encourage the redistribution of body fat away from "harmful" VAT sites and toward "safer" SCAT ones [ 74 — 76 ].

Thus, in this way, TZDs could allow for pushing the patient to below his CVATT. Paradoxically, the TZDs can lead to weight gain while improving insulin sensitivity as the new SCAT adipocytes continue to trap FA and as fat storage continues, eventually the new adipocytes will enlarge, become less insulin sensitive, and ultimately contribute to insulin resistance [ 77 ].

TZDs may also exert anti-inflammatory effects on adipocytes by reducing the production of serum amyloid A SAA and preventing the TNFα-mediated expression of adiponectin production [ 69 ].

Macrophages increase their accumulation within fat depots in direct proportion to increases in adipose tissue and adipocyte size. The increased macrophage activity observed in the adipose tissue of the obese may reflect a combination of conversion of local preadipocytes to macrophages and activation and recruitment of resident macrophages and circulating monocytes.

This seems to occur after the onset of adiposity but prior to insulin resistance, and supports the notion that pathophysiological consequences of obesity involve macrophages and inflammation that contribute to insulin resistance and metabolic syndrome [ 78 , 79 ].

Evidence suggests that macrophages and adipocytes not only express overlapping sets of genes and serve similar functions, but also commingle in the same part of the body — the fat tissue [ 80 ]. There are numerous inherent differences between VAT and SCAT.

VAT is a major predictor for insulin resistance [ 81 ] and metabolic syndrome [ 11 ]. Compared to SCAT, VAT adipocytes have a higher rate of lipolysis, which is more readily stimulated by catecholamines and less readily suppressed by insulin [ 82 ].

VAT also produces more IL-6 and plasminogen activator inhibitor-1 PAI-1 [ 81 ]. The "Portal Theory" suggests that insulin resistance and many of its related features could arise from VAT delivering free fatty acids FFAs at a high rate to the liver via the portal vein into which VAT directly drains [ 83 , 84 ].

This, in turn, would increase hepatic glucose production, reduce hepatic insulin clearance, and ultimately lead to insulin resistance, hyperinsulinemia, hyperglycemia as well as non-alcoholic fatty liver disease NAFLD.

FFA flux could also lead to enhanced production of triglycerides TGs and apolipoprotein B-rich lipoproteins, which are features of the insulin resistance syndrome [ 55 , 85 ]. Delivery of VAT derived pro-inflammatory cytokines may contribute to hepatic pathology such as non-alcoholic steatohepatitis NASH.

VAT also releases a large amount of glycerol which enters the liver where it can be converted to glucose, thereby contributing to hyperglycemia [ 86 ]. It is likely that the relationship observed between VAT and metabolic complications may not exclusively result from FFA flux from VAT into the portal vein and the portal theory does not adequately hold up as the sole explanation of the role of VAT in metabolic syndrome [ 7 ].

Recently, omental VAT cells have been shown to have an approximately two-fold higher rate of insulin-stimulated glucose uptake compared with SCAT adipocytes, and this could be explained by a higher GLUT-4 expression [ 87 ].

Perhaps in situations with a high intake of dietary glycemic load, a higher rate of glucose uptake and subsequently lipogenesis might be one mechanism by which TGs are stored preferentially in the VAT depot.

VAT is highly lipolytic and resistant to insulin's lipogenic effects yet apparently can remain insulin sensitive to glucose uptake. This efficiency in glucose uptake may reflect VAT's ability to accumulate and maintain its activity. Enhanced glucose utilization in VAT would be accompanied by less lipid oxidation, which would indirectly promote TG storage [ 87 ].

VAT has a high density of androgen receptors and testosterone which can amplify its own effect by up-regulation of androgen receptors, inhibiting the expression of lipoprotein lipase LPL and FA uptake [ 5 , 88 ].

In men, VAT is strongly negatively correlated with plasma total and free testosterone and sex-hormone binding globulin SHBG concentrations. Thus, in young men whose plasma total testosterone and free testosterone are high, the amount of VAT is low.

As men age, exceed their 20s, and reach middle age, their total and free testosterone decline, more fat is deposited in VAT stores, they often develop the "pot belly," and their risk for CHD increases [ 5 , 89 ]. The effects of testosterone on insulin resistance and metabolic syndrome risk factors are opposite in men and women [ 5 , 88 , 90 , 91 ].

Testosterone production often declines in women as they age, but VAT obesity in women is associated with elevated levels of total testosterone, free testosterone.

Hyperandrogenicity can also occur in polycystic ovary syndrome, where hyperinsulinemia can stimulate ovarian androgen production and suppress serum SHBG [ 88 , 93 ]. While weight loss in both sexes has been consistently shown to reverse the abnormalities in testosterone levels [ 94 — 97 ], a number of placebo controlled studies have consistently demonstrated that administering testosterone to obese men resulted in a significant reduction in VAT.

This occurred without significantly altering amounts of total body fat or lean body mass [ 89 , 98 — ]. However, the use of testosterone for VAT obesity is left open to debate [ 90 ]. Patients with type 2 diabetes and metabolic syndrome often appear Cushingoid, yet they invariably do not have elevated plasma cortisol [ ].

Compared to SCAT, VAT has more glucocorticoid receptors [ 88 ]. The enzyme β hydroxysteroid dehydrogenase type 1 β HSD1 converts inactive cortisone to the active compound cortisol, and, if overexpressed, may cause increases in local cortisol concentrations [ ].

Local production of active cortisol from inactive cortisone driven by β-HSD-1 activity is very high in VAT and barely detectable in SCAT.

Therefore it is likely that the VAT depot actively contributes to the production of high local concentrations of cortisol, which might not be reflected by plasma levels. These, in turn, might contribute to an increase in VAT accumulation [ ].

The amount of fat deposited within skeletal muscle intramyocellular lipid — IMCL and the ability of muscle to oxidize fat are important determinants of weight gain,[ ] weight regain following weight loss [ ], and the development of insulin resistance syndrome [ ].

IMCL and the VAT depot might not be independent from each other. Furthermore, the relationship between IMCL and insulin sensitivity is independent of percent total body fat and SCAT but not of VAT [ ]. In individuals with type 2 diabetes, among the depots of regional and overall adiposity, VAT was the depot of adipose tissue that was most strongly related to skeletal muscle insulin resistance [ ].

The researchers found that insulin sensitivity as well as postabsorptive rates of FFA utilization or oxidation by muscle were diminished in relation to VAT. Women with increased VAT did not have lower plasma FFA levels or lower rates for appearance of FFA, yet they had an impaired or reduced uptake of plasma FFA by the skeletal muscle in the leg [ ].

Together, this supports a role for VAT, IMCL lipid deposition, and perhaps impaired oxidation of nonadipose tissue lipid in insulin resistance and metabolic syndrome.

Mauriege et al found that adrenoreceptor sensitivity was increased in SCAT cells of individuals who have a higher VAT accumulation compared to those with a low VAT deposition [ ]. SCAT adipocytes from women with visceral obesity exhibit higher lipolysis rates in vitro than those obtained from women with little VAT [ ].

Mauriege et al also demonstrated that among men with high levels of VAT, SCAT adipocytes are more sensitive to β-adrenergic lipolysis which may further exacerbate an impaired insulin action, a potentially important factor in the etiology of metabolic syndrome associated with visceral obesity [ ].

Moreover, an increased truncal SCAT mass and an increased amount of VAT mass can independently predict insulin resistance [ ].

Together, these findings support that VAT may enhance central SCAT lipolysis and accelerate release of peripheral FFAs. The PPARs are important transcription factors that play an important role in the induction of adipose-specific genes, the proliferation and differentiation of adipocytes, and the development of mature adipose tissue.

A number of transcription factors are involved, including PPARγs. Giusti et al suggest that in VAT, the expression of PPARγ2 is controlled by local transcription factors RXRα, αSREBP1, and SREBP1c promoting fat storage in adipocytes.

Given that the fat storage capacity is limited in VAT, RXRα induces the expression of PPARγ2 in SCAT to increase its overall capacity [ ]. These data also suggest that the signal to promote fat storage may occur in VAT and that other metabolic and hormonal factors are involved in the control and modulation of adipogenesis in visceral fat [ ].

Perhaps the above can be explained as follows. SCAT cells may act as a buffer or sink for circulating FAs and TGs but once they reach their capacity they lose their protective benefits.

Initially, VAT may influence SCAT to expand and act as a buffer. However, once the critical VAT threshold CVATT is achieved and metabolic syndrome has begun to develop, then VAT may influence central SCAT to become more VAT-like, i. As discussed earlier, preadipocytes from SCAT depots have a greater capacity than VAT to differentiate into numerous, small, insulin-sensitive, adipocytes [ 70 , 71 ].

These lipid-storing cells act as a buffer or sink for circulating FAs and TGs, thereby preventing their deposition in non-adipose tissues, e. In defending the role of VAT accumulation in individuals with metabolic syndrome, we must postulate a high rate of lipid turnover, with high rates of lipolysis at certain times matched by high rates of lipid deposition at other times.

Otherwise, as Frayn points out, the hyperlipolytic VAT would ultimately disappear [ ]. He also suggests that if SCAT were to become insulin resistant, and therefore resistant to fat storage, then fat might tend to be deposited in VAT depots.

Another possibility is that the usually larger SCAT depot has a greater potential to contribute to insulin resistance through release of FFA into the systemic circulation. However, this would not adequately explain the subset of individuals who demonstrate metabolic profiles consistent with insulin resistance but are in fact lean, healthy-appearing with normal BMIs, excess VAT, little SCAT, and are referred to as "metabolically obese, normal weight MONW [ 26 ].

As described above, perhaps once VAT expands and SCAT depots reach their capacity for storing FAs, then do SCAT adipocytes become insulin resistant, release FFAs, and contribute to systemic insulin resistance and metabolic syndrome.

While some studies cast doubt on the portal theory and its implications for VAT's direct delivery of FFA to the liver [ , ], they leave open other mechanisms via which VAT could induce insulin resistance and other metabolic disturbances, e.

These will be discussed below. If trunk fat is taken into account, accumulation of fat in the hips and legs is an independent predictor of lower cardiovascular and diabetes-related mortality, and it seems to protect against impaired glucose metabolism, especially in women [ — ].

In a study of 1, women ages 60—85, those with excessive peripheral fat had less atherosclerosis determined by aortic calcification scores , and the quartile with both the highest amount of central fat and peripheral fat seemed to be partially protected by the high percentage of peripheral fat mass as reflected in a number of measured risk factors [ ].

These findings corroborate similar findings by the same group who followed postmenopausal women for 7. In yet another study, Tanko et al demonstrated that peripheral fat mass SCAT in generally obese, post-menopausal women is associated with increased adiponectin and higher insulin sensitivity [ ].

Together, these support protective roles for peripheral fat. In addition to fat trapping, these might include possible influences on adipokines, e. One must interpret these results with caution because the measuring technique of dual-energy X-ray absorptiometry DXA does not allow separate quantification of intermuscular and subcutaneous fat in the arms and legs as well as SCAT in the trunk [ ].

While VAT is a major predictor of insulin sensitivity in overweight and lean individuals [ , ], others have found abdominal SCAT to contribute to insulin resistance independently of VAT [ , ].

When there is an inability to store fat, due to lipodystrophy, the adipocytes' storage capacity is exceeded and lipids accumulate and cause lipotoxicity in liver, muscle, and other organ tissues [ 7 ]. A counterpart of lipodystrophy may be illustrated by patients with multiple symmetric lipomatosis MSL , a condition characterized by regional excess of subcutaneous adipose tissue.

These patients have higher adiponectin levels, a high degree of insulin sensitivity and glucose tolerance, very low lipid levels in liver and muscle cells, and markedly little VAT [ ]. In this case, SCAT may be protective and beneficial.

This may be analogous to thiazolidinedione action, which also promotes SCAT deposition while improving insulin sensitivity and glucose tolerance [ 74 , 75 ]. Estrogen promotes the accumulation of peripheral gluteo-femoral SCAT, which may be protective [ ].

The abundant presence of peripheral fat mass in generally obese women is associated with increased plasma adiponectin, and the loss of estrogen with menopause is associated with an increase in central fat [ ]. This accounts for the progression in many overweight women after menopause from a predominantly pear-shape or "gynoid" habitus to the apple or "android" shape.

Contrary to popular belief, menopause does not seem to independently cause a gain in total body weight; the increases in BMI that often accompany menopause are usually consistent with normal aging [ ]. However, even without weight gain, body fat distribution changes; postmenopausal obese women tend to accumulate abdominal fat along with deterioration of risk factors, even if total body weight and BMI do not change during menopause transition.

After menopause, when ovarian function declines, adipocytes become the primary source of endogenous estrogens [ ], and compared to "gynoid" or pear-shaped women, those with central obesity apple- or "android-" shaped have lower plasma SHBG and higher estradiol [ , ].

This suggests regional differences in the enzymatic conversion of steroid hormones in VAT versus SCAT [ , — ]. In ovarian hormone-deficient women, SCAT adipocyte size, lipoprotein lipase LPL activity, and basal lipolysis were not found to be significantly greater compared to regularly cycling premenopausal women.

For a given amount of total body fat, men have been found to have about twice the amount of VAT than what is found in premenopausal women but this may change after menopause when VAT storage becomes predominant [ , ].

Along with an increase in VAT, a decline in estrogen is also associated with reduced lean body mass as well as other features of the metabolic syndrome including: dyslipidemia with elevation in Lp a , triglycerides, and an increase in small, dense, LDL particles.

Estrogen deficiency also may influence cardiac risk by its effects on the insulin action, the arterial wall, and fibrinolysis. Park et al showed that postmenopausal women lost less VAT compared with the premenopausal women during a weight reduction program The reasons behind this are presently unclear.

As mentioned above, in menopause, adipocytes are primary sources of endogenous estrogens in women [ , ], and estrogens are known inhibitors of IL-6 secretion [ ]. It is worth noting that the relationship between BMI and serum IL-6 was observed only in postmenopausal women, and this relationship was lost among those women receiving hormone replacement [ ].

Adipose tissue-derived estrogens in postmenopausal women would not be sufficient to reduce IL-6 in a similar way as endogenous estrogens do in premenopausal women [ ]. Perhaps in premenopausal women, endogenous estrogen from the ovaries helps keep VAT volume relatively low and is thereby protective.

Estrogen by itself seems to protect postmenopausal women receiving replacement therapy from VAT accumulation, and in women with type 2 diabetes, estrogen replacement may protect against the risk of cardiac events [ , ]. Compared to men of similar age, premenopausal women appear to be significantly protected from CHD.

However, by age 70 the incidence of CHD is equal in men and women, suggesting that estrogen deficiency causes a rapid acceleration in CHD risk [ ]. Yet, in elderly, postmenopausal women, Tanko et al showed that those women with higher amounts of central versus peripheral obesity had significantly higher levels of estradiol and lower adiponectin.

This suggests that prolonged and increased exposure of SCAT cells to estradiol may eliminate the protective effect of SCAT by affecting SCAT's ability to release adiponectin thereby promoting the atherogenic effects of IL-6 [ ].

Perhaps future research will help clarify whether central obesity has any implication for increased susceptibility to the adverse cardiovascular effects of hormone replacement therapy HRT in diabetic patients early after initiation of therapy [ ].

Obesity, particularly visceral obesity, as well as insulin resistance and hyperinsulinemia are associated with breast cancer [ ]. Insulin may increase estrogen action by increasing bioavailable estrogen due to a decrease in sex hormone-binding globulin, by influencing estrogen receptors, and by increasing aromatization of androgen to estrogen at the tissue level, a phenomenon which has been demonstrated in breast tissue.

Estrogen upregulates the IGF-1 receptor and IGFBP-1 and -2 and may directly activate the IGF-1 receptor, thereby increasing insulin signaling [ ]. Around , most women died soon after menopause. The average lifespan of persons in the United States has since lengthened by greater than 30 years [ ], which means that women, and men, too, are now spending 30 or more years with hormonal and physiological states that society and medicine has not had to deal with previously.

These, combined with significant dietary and lifestyle changes since , must be considered as critical contributing factors to the world's current epidemic of metabolic syndrome. When one consumes too many calories, especially in the form of excessive carbohydrates, the liver converts excess glucose to fatty acids.

First, glucose that is not oxidized or stored as glycogen is metabolized to acetyl CoA, which then enters the lipogenic pathway. Acetyl CoA is catalyzed to form malonyl CoA, which in turn inhibits carnitine palmitoyl transferase 1 CPT-1, the enzyme responsible for fatty acid transport into the mitochondria [ 42 ].

The net effect is that malonyl CoA from excess carbohydrates, glucose, and insulin reduces the oxidation of FAs [ ]. This results in increased accumulation of intracellular fat in the form of long chain fatty acids and their derivatives, e. Cellular TG accumulation is not initially toxic and may actually be protective by diverting excess FAs from pathways that lead to cytotoxicity [ ].

While glucose is being preferentially utilized, the FAs are metabolized by pathways other than their preferred β oxidation, leading to toxic products, e. The subsequent development of the cell's resistance to insulin-mediated glucose uptake, which prevents further influx of glucose, may be viewed as being protective in that it limits the amount of intracellular glucose to be preferentially metabolized over the β oxidation of intracellular FAs [ 29 , 37 , ].

The cell can be insulin resistant with respect to glucose uptake and metabolism but remain sensitive to insulin's lipogenic effects and the de novo synthesis of fat.

Overconsumption of calories, especially in the form of carbohydrates, also stimulates hyperinsulinemia that can then upregulate SREBP-1c and increase de novo lipogenesis [ 43 ].

The first adipocyte-specific hormone to be characterized, leptin is produced predominantly by SCAT adipocytes compared to VAT. Females produce leptin at about twice the rate in males [ ], and leptin secretion increases with enlarged adipocyte cell size. Circulating leptin rises by 40 percent after acute overfeeding and more than three-fold after chronic overfeeding, whereas fasting is associated with decreased leptin levels [ ].

The increase in leptin concentration after meals is not simply a result of a caloric load, but is in response to a signal that is not present following a fat load without carbohydrate [ ].

Leptin circulates in a free form and is also bound to a soluble leptin receptor — sOBR, which is positively associated with energy intake from carbohydrates and negatively associated with energy intake from dietary fat [ ].

Excess caloric consumption and fat deposition results in newly synthesized FAs that are transported as VLDLs and stored as TG in adipocytes.

Initially, these expanding adipocytes secrete leptin in proportion to their growing fat accumulation. Leptin also crosses the blood brain barrier, stimulates its receptor in the hypothalamus, and causes the release of neuropeptide-Y NP-Y , which reduces feeding behavior [ 85 ].

This, in turn, suppresses appetite and stimulates thyroid function. Leptin affects peripheral tissues, and is a determinant of insulin sensitivity. The ensuing hyperleptinemia increases fat oxidation in skeletal muscle [ — ], and also keeps de novo lipogenesis in check by lowering the involved transcription factor, i.

It promotes cholesterol ester synthesis in macrophages in a hyperglycemic environment, an important process in the formation of foam cells in atherosclerosis which may suggest a protective role of relative leptin resistance [ ]. Leptin also possibly increases sympathetic nervous system SNS activity with subsequent decreased FFA oxidation and thermogenesis [ ].

All of these effects of leptin tend to limit further weight gain. As the process progresses, inefficient leptin action can lead to the opposite of leptin's protective effects, e. Subsequently, plasma leptin levels rise.

The majority of obese individuals with high leptin levels show a leptin insensitivity or "resistance [ ]," which occurs at the leptin receptor level.

In animal models, leptin-resistance and leptin-deficiency increases, and upregulates the hepatic expression of SREBP-1c mRNA, which may stimulate an increase in fat production via de novo lipogenesis.

Together, all of these features suggest a state of "leptin resistance" which may ultimately lead to obesity and metabolic syndrome [ 29 , ].

It is quite possible that hyperleptinemia in diet-induced obesity serves to protect nonadipose tissues e. muscles, liver, pancreatic β cells, and myocardium from the toxic effects resulting from the spillover of full adipose stores and subsequent ectopic deposition of FFAs.

In defense of this paradigm, Unger points out that normally rats can tolerate a 60 percent fat diet because 96 percent of the surplus fat is stored in an enlarging adipose tissue mass, in which leptin gene expression increases proportionally [ ]. However, when leptin is congenitally absent or inactive, or ineffective due to resistance, even on a normal or low-fat diet, excess dietary fat is deposited in nonadipose tissues.

This causes dysfunction lipotoxicity , and possible cell death lipoaptosis [ 29 ]. Acquired leptin resistance occurs in aging, obesity, Cushing's syndrome, and acquired lipodystrophy, a condition associated with protease inhibitor therapy of AIDS.

Preliminary evidence suggests that patients with these conditions have increased ectopic fat, i. The relation between cerebrospinal fluid and serum levels of leptin in obese humans suggests that defective blood brain barrier BBB transport accounts for a great deal of leptin resistance in the CNS.

Banks et al showed in mice that serum TGs directly inhibit the transport of leptin across the BBB and so could be a major cause of leptin resistance across the central nervous system CNS. Thus they suggest that serum TGs are likely a major cause of the leptin resistance seen in both obesity and starvation [ ].

This hypothesis explains why lowering TGs may be therapeutically useful in enhancing the effects of leptin. Compared to VAT, SCAT is the predominant source of leptin [ 60 ], yet patients with VAT obesity may tend to have higher leptin levels than normal, lean individuals but lower than those with predominantly SCAT or subcutaneous obesity [ 29 ].

This suggests that the hyperleptinemia of predominantly VAT obesity is not high enough to overcome a leptin resistance due to the accumulation of ectopic fat in nonadipose tissues, which leads to lipotoxicity and ultimately the metabolic syndrome [ 29 ].

A number of clinical states exhibit evidence of leptin insufficiency, either leptin deficiency or resistance, and they all have in common the metabolic syndrome. These include rare genetic diseases known as lipodystrophies, which are characterized by a redistribution of fat. Ironically, in the more severe cases, e.

There is hyperleptinemia along with hyperphagia and a predominance of intra-muscular fat [ ]. Dunnigan-type familial partial lipodystrophy is a rare autosomal dominant condition characterized by markedly reduced plasma leptin levels along with gradual loss of SCAT from the extremities, trunk, and gluteal region, commencing at the time of puberty, as well as hyperinsulinemia, glucose intolerance, dyslipidemia high TGs with low HDL , and diabetes [ , ].

These individuals do maintain central obesity and VAT [ ], which supports a relatively protective role for SCAT and implicates VAT as being more pathogenic. The aforementioned potential role of TGs in leptin resistance may have implications for patients with lipodystrophy and lipoatrophy who have little or no fat mass, and as a result, have very little or no leptin.

Basal metabolic rate BMR The BMR refers to the amount of energy your body needs to maintain homeostasis. Factors that affect our BMR Your BMR is influenced by multiple factors working in combination, including: Body size — larger adult bodies have more metabolising tissue and a larger BMR.

Amount of lean muscle tissue — muscle burns kilojoules rapidly. Crash dieting, starving or fasting — eating too few kilojoules encourages the body to slow the metabolism to conserve energy.

Age — metabolism slows with age due to loss of muscle tissue, but also due to hormonal and neurological changes. Growth — infants and children have higher energy demands per unit of body weight due to the energy demands of growth and the extra energy needed to maintain their body temperature.

Gender — generally, men have faster metabolisms because they tend to be larger. Genetic predisposition — your metabolic rate may be partly decided by your genes.

Hormonal and nervous controls — BMR is controlled by the nervous and hormonal systems. Hormonal imbalances can influence how quickly or slowly the body burns kilojoules.

Environmental temperature — if temperature is very low or very high, the body has to work harder to maintain its normal body temperature, which increases the BMR.

Infection or illness — BMR increases because the body has to work harder to build new tissues and to create an immune response. Amount of physical activity — hard-working muscles need plenty of energy to burn. Regular exercise increases muscle mass and teaches the body to burn kilojoules at a faster rate, even when at rest.

Drugs — like caffeine or nicotine , can increase the BMR. Dietary deficiencies — for example, a diet low in iodine reduces thyroid function and slows the metabolism.

Thermic effect of food Your BMR rises after you eat because you use energy to eat, digest and metabolise the food you have just eaten. Hot spicy foods for example, foods containing chilli, horseradish and mustard can have a significant thermic effect.

Energy used during physical activity During strenuous or vigorous physical activity, our muscles may burn through as much as 3, kJ per hour. Metabolism and age-related weight gain Muscle tissue has a large appetite for kilojoules.

Hormonal disorders of metabolism Hormones help regulate our metabolism. Thyroid disorders include: Hypothyroidism underactive thyroid — the metabolism slows because the thyroid gland does not release enough hormones.

Some of the symptoms of hypothyroidism include unusual weight gain, lethargy, depression and constipation. Hyperthyroidism overactive thyroid — the gland releases larger quantities of hormones than necessary and speeds the metabolism.

Some of the symptoms of hyperthyroidism include increased appetite, weight loss, nervousness and diarrhoea. Genetic disorders of metabolism Our genes are the blueprints for the proteins in our body, and our proteins are responsible for the digestion and metabolism of our food.

Some genetic disorders of metabolism include: Fructose intolerance — the inability to break down fructose, which is a type of sugar found in fruit, fruit juices, sugar for example, cane sugar , honey and certain vegetables. Galactosaemia — the inability to convert the carbohydrate galactose into glucose.

Galactose is not found by itself in nature. It is produced when lactose is broken down by the digestive system into glucose and galactose. Sources of lactose include milk and milk products, such as yoghurt and cheese.

Phenylketonuria PKU — the inability to convert the amino acid phenylalanine into tyrosine. High levels of phenylalanine in the blood can cause brain damage. High-protein foods and those containing the artificial sweetener aspartame must be avoided.

Where to get help Your GP doctor Dietitians Australia External Link Tel. Metabolic disorders External Link , MedlinePlus, National Library of Medicine, National Institutes of Health, USA.

Rolfes S, Pinna K, Whitney E , 'Understanding normal and clinical nutrition' External Link , Cengage Learning, USA. Dietary energy External Link , National Health and Medical Research Council NHMRC and Department of Health and Aged Care, Australian Government.

Severe burn-injured patients often experience chronic inflammation and associated metabolic dysfunction Jeschke et al. Such chronic hyper-inflammation often affects wound healing, triggers WAT browning, lipolysis, lipotoxicity, sepsis, and associated multi-organ failure complications.

Research over the past two decades has shown that inflammation in WAT is a major contributing factor in the hypermetabolic response observed in burn patients.

WAT acts as an endocrine organ and plays an active role in secreting inflammatory moieties such as cytokines, hormones, and other growth factors. Under critical stress, adipocytes recruit inflammatory mediators, chemo-attractants such as monocyte chemoattractant protein-1 or MCP-1 and cytokines that activate macrophage polarization as well as multiple metabolic signaling pathways.

It is established that burn injury results in structural, functional, and morphological changes in WAT, with enhanced levels of circulating WAT-derived adipokines, inflammatory mediators and hormones that are known to regulate WAT inflammation and metabolism Jeschke et al.

Studies in human patients and rodents have shown that neutralization of TNFα accelerates wound healing Ashcroft et al. Assessment of WAT collected from burn patients revealed the enhanced leukocyte infiltration, macrophages, and activation of Nod-like inflammasome receptor-3 NLRP3 protein that plays a crucial role in multiple signaling pathways Stanojcic et al.

Furthermore, studies elucidating the role of NLRP3 in WAT after burn injury shows that NLRP3 has an anti-browning effect and that genetic deletion of this inflammasome augments WAT browning and the hypermetabolic response Vinaik et al.

Macrophage recruitment in WAT, on the other hand, undergoes alternate polarization and activation leading to the secretion of catecholamines and cytokines which induce multiple signaling cascades Abdullahi et al. For example, alternatively activated macrophages secrete IL6 that plays a crucial role in activating WAT browning and associated dysfunction post-burn injury Ashcroft et al.

Moreover, inhibition of alternatively activated macrophages impairs metabolic adaptation and the thermogenic response of adipose tissue. Furthermore, administration of interleukin-4 reinstates thermogenic gene expression, systemic fat mobilization and energy homeostasis in response to cold Nguyen et al.

Therapeutic interventions targeting β-adrenergic receptors, cytokines, WAT lipolysis, and browning mediators after burn injury have shown promising results in improving REE, hepatic steatosis, reducing hyperglycemia, hyperlipidemia, and chronic inflammation. Propranolol, a non-selective β-adrenergic signaling blocker, has shown promising benefits in reducing REE and reduction in the expression of browning markers Ucp1 , Cox-iv in WAT, suggesting the importance of regulating catecholamines and stress hormones to mitigate WAT-associated dysfunction Sidossis et al.

Propranolol has higher affinity toward β1 and β2 receptors Barbe et al. However, studies conducted by an independent research group has shown that chronic adrenergic stress post-burn injury upregulates β3 receptor expression in WAT albeit its role in WAT browning remains elusive Saraf et al.

Also, studies in pediatric burn patients treated with propranolol by an independent group has shown a decrease in cardiac workload accompanied by reduced lipolysis, muscle catabolism, hepatosteatosis, and ultimately REE Finnerty and Herndon, However, the non-selective nature of propranolol also exposes patients to a significant risk of cardiac failure Unpublished clinical data.

Furthermore, systemic IL6 levels were found upregulated in burn patient samples soon after burn injury and persisted for more than a month Patsouris et al. Subsequent studies assessing the role of IL6 in WAT using the global IL6 knockout mice model has shown that deletion of IL6 prevents WAT browning after burn injury Abdullahi et al.

Also, IL6 deletion reduces infiltration of macrophages and inhibits alternative activation and polarization of macrophages Abdullahi et al. Metformin, a successful clinical drug for use against diabetes has shown promising results in improving insulin resistance without causing hypoglycemia in phase II randomized clinical trials conducted in burn patients Jeschke et al.

Mechanistic studies in a murine model of thermal injury assessing the action of metformin has demonstrated that metformin induces protein phosphatase 2A PP2A activity, thus dephosphorylating key enzymes in the WAT lipolytic pathway [such as acetyl-CoA carboxylase ACC and HSL] and promoting fat storage in adipocytes Auger et al.

In fact, metformin treatment also reduces mitochondrial respiration and enhances mitochondrial coupling control in WAT, suggesting an indirect protective effect of metformin in reducing WAT browning and REE Auger et al. While these changes are independent of adenosine monophosphate kinase AMPK activation, the canonical mechanism of metformin, the authors postulate that higher concentrations of this biguanide would be necessary to activate this signaling pathway in highly energetic beige adipose Auger et al.

Additionally, another clinical study assessing metformin has shown promising results against skeletal muscle catabolism and insulin resistance following severe burn injury Gore et al.

Furthermore, studies assessing the impact of metformin on inflammation in adipocytes has revealed that metformin administration suppresses pro-inflammatory cytokines such as TNFα and IL-1β and also, indirectly enhances the anti-inflammatory effect of metformin Qi et al.

Moreover, in burn patients there is evidence that this biguanide can decrease inflammatory mediators in the serum such as IL-1β and MCP-1 Jeschke et al.

To date, the potential benefits of other biguanides or PPARγ agonists such as thiazolidinediones on glucose control and systemic dysfunction post-burn have not been adequately explored. Acipimox, a niacin derivative that targets WAT lipolysis, has shown effective results in a murine model when challenged with severe burn injury.

Acipimox not only reduced systemic lipid levels, in fact, it also attenuated WAT browning and hepatic fat infiltration after burn injury Barayan et al. Additionally, acipimox has shown promising results in 3-month clinical trials in HIV-infected patients 23 with hyperlipidemia, and abnormal fat distribution.

Acipimox treatment resulted in reduced systemic lipid levels, decreased WAT lipolysis and enhanced insulin sensitivity in HIV-infected patients Hadigan et al.

However, the impact of acipimox on WAT inflammation and systemic glucose metabolism in these adverse events has yet to be elucidated.

Adipose tissue has an enormous buffering capacity for release, storage, and dissipating energy in times of need. Research over recent years has made it clear that adipose tissue function and dysfunction has a major role to play in burn injury and its associated hypermetabolic response which often progresses to multi-organ dysfunction Figure 2.

Being an endocrine organ, the adipose tissue secretes a myriad of adipokines and maintains energy homeostasis in humans. Although significant success has been achieved in understanding the factors that trigger adipocyte dysfunction, our knowledge is still limited to the tip of an iceberg.

Much of the research in the field has focused on identifying the key markers being altered when challenged by burn injury. Although the role of insulin has been thoroughly covered, there are a plethora of cytokines, adipokines leptin, adiponectin and stress hormones that are still not fully understood and how they affect insulin action and WAT morphology is still a matter of debate.

Figure 2. Adipose dysfunction and associated multi-organ damage after burn injury. Elevated levels of systemic FFA flux, inflammatory mediators and adipokines collectively contribute to a feed-forward loop, hypermetabolism, and multi-organ damage Jeschke et al.

Macrophage infiltration and polarization in adipose tissue after burn injury is known, however, the exact role of inflammatory mediators is still not clear.

Studies elucidating the role of IL6 and its inhibition have revealed the detrimental role of this cytokine in the processes of WAT browning and hepatic steatosis Abdullahi et al. However, its role in macrophage recruitment and polarization is not clear Abdullahi et al.

Similarly, studies conducted to understand the role of TNFα in burn patients have revealed that it is upregulated after burn injury Yeh et al. Research studies conducted in the NLRP3 murine model have demonstrated that deleting NLRP3 augments WAT browning, lipolysis, hepatic steatosis and impairs wound healing Stanojcic et al.

However, further research studies are required to understand the protective role and mechanistic action of NLRP3 when challenged with burn injury.

Research over the past decade and advances in clinical burn care have significantly advanced our knowledge and greatly improved the survival of burn patients Figure 3.

Interventions such as metformin have shown promising safety and efficacy in phase II clinical trials. Moreover, metformin protects against WAT lipolysis, browning, and helps in maintaining euglycemia.

Further detailed clinical investigation is, however, required to elucidate its effect on adipose tissue function after severe burn injury. Recently, the WAT lipolysis inhibitor acipimox has shown promising results in rodent studies when challenged with burn injury, suggesting the possible benefits of targeting WAT dysfunction in the future.

However, further mechanistic studies are required to elucidate the action of acipimox and its possible impact on insulin sensitivity and WAT inflammation. The strong correlation of these drugs targeting WAT dysfunction suggests that reducing WAT lipolysis and browning is an important therapeutic strategy for the treatment of the hypermetabolic response in burn patients.

Other potentially relevant strategies could be understanding the role of macrophage recruitment in WAT and mechanisms involved in activation and polarization of macrophages. To that effect, much remains to be uncovered with regards to the interactions of macrophages with themselves and the interaction of macrophages with adipocytes when challenged with burn injury.

Lastly, understanding the role of adipokines and their impact on signaling pathways in vital target organs such as the brain, central nervous system, heart, liver, and skeletal muscle, can possibly reveal novel therapeutic strategies in reducing the WAT-associated hypermetabolic response in burn patients.

Figure 3. Summary of the therapeutic advances targeting adipocyte lipolysis and browning post-burn injury. Metabolic impact of drug treatment A Propranolol B Tocilizumab C Metformin D Acipimox post-burn injury. All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

The authors received no particular funding for this work. The grants supporting the research work are Canadian Institute of Health Research , NIH R01GM and R01GM and Ontario Institute of regenerative medicine. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Abdullahi, A. Alternatively activated macrophages drive browning of white adipose tissue in burns. doi: PubMed Abstract CrossRef Full Text Google Scholar. IL-6 signal from the bone marrow is required for the browning of white adipose tissue post burn injury.

Shock 47, 33— Taming the flames: targeting white adipose tissue browning in hypermetabolic conditions. Browning of white adipose tissue after a burn injury promotes hepatic steatosis and dysfunction. Cell Death Dis. Ahima, R. Adipose tissue as an endocrine organ. Trends Endocrinol. CrossRef Full Text Google Scholar.

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Circulation , — Ashcroft, G. Tumor necrosis factor-alpha TNF-alpha is a therapeutic target for impaired cutaneous wound healing. Wound Repair Regen. Auger, C. Metformin prevents the pathological browning of subcutaneous white adipose tissue. Google Scholar.

The biochemical alterations underlying post-burn hypermetabolism. Acta Mol. Basis Dis. Barayan, D. Inhibition of lipolysis with acipimox attenuates post-burn white adipose tissue browning and hepatic fat infiltration.

Shock 53, — Barbatelli, G. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation.

Barbe, P. In situ assessment of the role of the beta 1-, beta 2- and beta 3-adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue.

Barrett, L. Understanding acute burn injury as a chronic disease. Burns Trauma Barrow, R. The use of beta-adrenergic blockade in preventing trauma-induced hepatomegaly.

Bartelt, A. Adipose tissue browning and metabolic health. Belfort, R. Dose-response effect of elevated plasma free fatty acid on insulin signaling. Diabetes 54, — Berlan, M. The alpha 2-adrenergic receptor of human fat cells: comparative study of alpha 2-adrenergic radioligand binding and biological response.

Paris 78, — Bhattarai, N. Brown adipose tissue recruitment in a rodent model of severe burns. Burns in press. Boura-Halfon, S.

Phosphorylation of IRS proteins, insulin action, and insulin resistance. Burks, D. IRS proteins and beta-cell function. Diabetes 50 Suppl. Carter, E. Effects of burn injury, cold stress and cutaneous wound injury on the morphology and energy metabolism of murine brown adipose tissue BAT in vivo.

Life Sci. Association of heat production with 18F-FDG accumulation in murine brown adipose tissue after stress. Cho, K. Signaling pathways implicated in alpha-melanocyte stimulating hormone-induced lipolysis in 3T3-L1 adipocytes.

Cell Biochem. Coelho, M. Biochemistry of adipose tissue: an endocrine organ. Dodd, G. Leptin and insulin act on POMC neurons to promote the browning of white fat. Cell , 88— Endo, T. Fasshauer, M. Adipokines in health and disease. Trends Pharmacol.

Finnerty, C.

Targeting senescent cells enhances adipogenesis and metabolic function in old age It promotes adaptive responses including those causing muscles to increase their use of lipid stores rather than relying primarily on carbohydrate reserves. doi: A study reports that eating capsaicin boosts metabolic rate modestly. In: Ferri's Clinical Advisor Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV: Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. How Much Physical Activity Do I Need? Spatial binning of the fluorescence decay defines how many immediate adjacent pixels are combined before the lifetime is calculated.
How to Speed Up Your Metabolism: 8 Easy Ways Estrogens increase funcion of Enhanced metabolic function High cholesterol prevention protein 8b functon brown adipose tissue of mice. Evidence Enhanced metabolic function plasticity. Medical News Today. However, we can make metabolism work for us when we exercise. Garg A, Peshock RM, Fleckenstein JL: Adipose tissue distribution pattern in patients with familial partial lipodystrophy Dunnigan variety.
Actions for this page ,etabolic is true that Protein intake for better athletic performance burn more calories when you exercise meetabolic, especially when you get your Enhancfd rate up with activities like biking metaboliv swimming. Enhanced metabolic function authors Performance-enhancing foods reviewed Enhanced metabolic function edited the paper. The Enhanced metabolic function ratio Funcgion not show significant changes compared Enhanced metabolic function the baseline after FCCP injection which has been reported previously 32 Sako D Grinberg AV Liu J Davies MV Castonguay R Maniatis S Andreucci AJ Pobre EG Tomkinson KN Monnell TE Ucran JA Martinez-Hackert E Pearsall RS Underwood KW Seehra J Kumar R Characterization of the ligand binding functionality of the extracellular domain of activin receptor type IIb The Journal of Biological Chemistry — To confirm that fluorescence lifetime changes were based on cellular metabolism rather than changes in pH induced by the injection of pharmacological reagents; pH-meter measurements showed that none of the reagents resulted in a significant change of the pH-value of the media Supplementary Table 2 and Note 6. Nevertheless, the MCR did not change due to an equal fluorescence intensity increase of mitochondrial NADH.
Thank you for Enhanced metabolic function nature. You are using metabollc browser version with Enhancd support for CSS. Enhanced metabolic function obtain the best experience, we recommend you use fnuction Enhanced metabolic function up Reduce cravings slimming pills date browser or turn mtabolic compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Fluorescence lifetime imaging microscopy FLIM of intrinsic fluorophores such as nicotinamide adenine dinucleotide NADH allows for label-free quantification of metabolic activity of individual cells over time and in response to various stimuli, which is not feasible using traditional methods due to their destructive nature and lack of spatial information.

Enhanced metabolic function -

If you are over 40 years of age, have a pre-existing medical condition or have not exercised in some time, see your doctor before starting a new fitness program. Hormones help regulate our metabolism. Some of the more common hormonal disorders affect the thyroid.

This gland secretes hormones to regulate many metabolic processes, including energy expenditure the rate at which kilojoules are burned. Thyroid disorders include:. Our genes are the blueprints for the proteins in our body, and our proteins are responsible for the digestion and metabolism of our food.

Sometimes, a faulty gene means we produce a protein that is ineffective in dealing with our food, resulting in a metabolic disorder. In most cases, genetic metabolic disorders can be managed under medical supervision, with close attention to diet.

The symptoms of genetic metabolic disorders can be very similar to those of other disorders and diseases, making it difficult to pinpoint the exact cause.

See your doctor if you suspect you have a metabolic disorder. Some genetic disorders of metabolism include:. This page has been produced in consultation with and approved by:. Content on this website is provided for information purposes only.

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All users are urged to always seek advice from a registered health care professional for diagnosis and answers to their medical questions and to ascertain whether the particular therapy, service, product or treatment described on the website is suitable in their circumstances.

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Actions for this page Listen Print. Summary Read the full fact sheet. On this page. What is metabolism? Two processes of metabolism Metabolic rate Metabolism and age-related weight gain Hormonal disorders of metabolism Genetic disorders of metabolism Where to get help. Two processes of metabolism Our metabolism is complex — put simply it has 2 parts, which are carefully regulated by the body to make sure they remain in balance.

They are: Catabolism — the breakdown of food components such as carbohydrates , proteins and dietary fats into their simpler forms, which can then be used to provide energy and the basic building blocks needed for growth and repair.

Anabolism — the part of metabolism in which our body is built or repaired. Anabolism requires energy that ultimately comes from our food. When we eat more than we need for daily anabolism, the excess nutrients are typically stored in our body as fat.

Thermic effect of food also known as thermogenesis — your body uses energy to digest the foods and drinks you consume and also absorbs, transports and stores their nutrients. Energy used during physical activity — this is the energy used by physical movement and it varies the most depending on how much energy you use each day.

Physical activity includes planned exercise like going for a run or playing sport but also includes all incidental activity such as hanging out the washing, playing with the dog or even fidgeting! Basal metabolic rate BMR The BMR refers to the amount of energy your body needs to maintain homeostasis.

Factors that affect our BMR Your BMR is influenced by multiple factors working in combination, including: Body size — larger adult bodies have more metabolising tissue and a larger BMR.

Amount of lean muscle tissue — muscle burns kilojoules rapidly. Crash dieting, starving or fasting — eating too few kilojoules encourages the body to slow the metabolism to conserve energy. Age — metabolism slows with age due to loss of muscle tissue, but also due to hormonal and neurological changes.

Growth — infants and children have higher energy demands per unit of body weight due to the energy demands of growth and the extra energy needed to maintain their body temperature.

Gender — generally, men have faster metabolisms because they tend to be larger. Genetic predisposition — your metabolic rate may be partly decided by your genes. Hormonal and nervous controls — BMR is controlled by the nervous and hormonal systems.

Hormonal imbalances can influence how quickly or slowly the body burns kilojoules. Environmental temperature — if temperature is very low or very high, the body has to work harder to maintain its normal body temperature, which increases the BMR.

Infection or illness — BMR increases because the body has to work harder to build new tissues and to create an immune response. Amount of physical activity — hard-working muscles need plenty of energy to burn.

Regular exercise increases muscle mass and teaches the body to burn kilojoules at a faster rate, even when at rest. Drugs — like caffeine or nicotine , can increase the BMR. Dietary deficiencies — for example, a diet low in iodine reduces thyroid function and slows the metabolism.

Thermic effect of food Your BMR rises after you eat because you use energy to eat, digest and metabolise the food you have just eaten. Hot spicy foods for example, foods containing chilli, horseradish and mustard can have a significant thermic effect. Energy used during physical activity During strenuous or vigorous physical activity, our muscles may burn through as much as 3, kJ per hour.

Metabolism and age-related weight gain Muscle tissue has a large appetite for kilojoules. Hormonal disorders of metabolism Hormones help regulate our metabolism. Thyroid disorders include: Hypothyroidism underactive thyroid — the metabolism slows because the thyroid gland does not release enough hormones.

Some of the symptoms of hypothyroidism include unusual weight gain, lethargy, depression and constipation. Hyperthyroidism overactive thyroid — the gland releases larger quantities of hormones than necessary and speeds the metabolism.

Some of the symptoms of hyperthyroidism include increased appetite, weight loss, nervousness and diarrhoea. Genetic disorders of metabolism Our genes are the blueprints for the proteins in our body, and our proteins are responsible for the digestion and metabolism of our food.

Altogether, these data show that Cebpb ΔuORF mice are protected against steatosis in the liver and other organs in response to HFD. Histological sections of liver from A males and B females of wt or Cebpb ΔuORF mice ΔuORF 19 weeks.

Sections were stained with hematoxylin blue and Sudan III males or Oil-Red-O females for red color lipid staining.

Chronic obesity often results in the loss of glucose homeostasis Abranches et al. We therefore analyzed glucose tolerance and insulin sensitivity in the HFD fed Cebpb ΔuORF mice and wt littermates. Glucose clearance from the circulation measured by intraperitoneal glucose tolerance test IPGTT was impaired in response to 7 weeks HFD feeding for the wt mice of both sexes, as is shown by a significantly increased area under the curve AUC Figure 6A, B.

For the Cebpb ΔuORF male mice, the already significantly better glucose clearance on normal diet does not change on HFD Figure 6A. The female Cebpb ΔuORF mice on HFD show reduced glucose clearance in the IPGTT compared to ND but they perform significantly better than the HFD fed wt females Figure 6B.

At the time of 7 weeks on HFD, both the wt and Cebpb ΔuORF mice of both sexes did not develop insulin insensitivity as measured by intraperitoneal insulin sensitivity test IPIST Figure 6C, D. Both the Cebpb ΔuORF males and females, however, generally performed better on IPIST than the wt mice.

Intraperitoneal glucose tolerance test IPGTT with the calculated area under the curve AUC of Cebpb ΔuORF A male and B female ΔuORF and wt mice injected i. Intraperitoneal insulin sensitivity test IPIST with the calculated area under the curve AUC of Cebpb ΔuORF C male and D female ΔuORF mice and wt mice injected i.

with insulin 0. In conclusion, our data show that Cebpb ΔuORF mice on HFD feeding perform better in a glucose tolerance test, are protected against steatosis and show a lower inflammatory status of WAT, although the latter is less evident in females.

These metabolically favorable phenotypes of the Cebpb ΔuORF mice correlate with hyperplastic fat storage and in male mice with more efficient fat accumulation in the subcutaneous depot.

In wt male mice all four transcripts are significantly lower expressed on HFD compared to ND Figure 7A. This generally corresponds to their protein levels as determined by immunoblotting, although the expression of PPARγ and SREBP1c varies considerably between the mice Figure 7—figure supplement 1A.

For the wt female mice, only the transcript levels of FAS were downregulated upon HFD and for Cebpb ΔuORF mice only expression of PPARγ and FAS was significantly higher on HFD compared to wt females on HFD Figure 7B.

The better maintained expression of FAS in HFD fed Cebpb ΔuORF females in the qPCR analysis however could not be recapitulated with immunoblotting Figure 7—figure supplement 1B. In wt males, both LAP and LIP isoforms were upregulated upon HFD feeding as shown in the immunoblot Figure 8A and determined by quantification of blot signals from a cohort Figure 8B, C.

For the females, a significant increase in both LAP and LIP expression in response to HFD feeding was only observed in the Cebpb ΔuORF mice Figure 8D, F.

In two previous reports, we have shown that Cebpb ΔuORF mice display metabolic improvements and a delay in the onset of age-related conditions, collectively resulting in an extended lifespan in females Müller et al.

Here, we demonstrate that Cebpb ΔuORF mice are protected against the development of metabolic disturbances in response to HFD feeding. In males, this improved metabolic phenotype occurs although the total fat mass in Cebpb ΔuORF mice is increased in response to HFD to a greater extent than in wt mice.

Our data indicate that two special features of the white adipose tissue WAT in Cebpb ΔuORF males contribute to these metabolic improvements. Firstly, Cebpb ΔuORF males on a HFD store the surplus of nutrients in fat depots that expand through hyperplasia; they increase the number of adipocytes and thus the individual cells have to store less fat.

These smaller adipocytes are metabolically more active and less inflamed compared to the inflated wt adipocytes residing in a hypertrophic fat depot. Hypertrophic adipocytes are known to secrete inflammatory cytokines that promote insulin resistance and other metabolic disturbances Reilly and Saltiel, ; Weisberg et al.

Furthermore, since the number of adipocytes in hypertrophic fat tissue does not increase and the amount of fat that can be stored in an adipocyte is limited, fat starts to accumulate in ectopic tissues like liver or muscle, compromising metabolic health Frasca et al.

Accordingly, in wt males on HFD we observed pronounced inflammation and macrophage infiltration in the visceral WAT and severe steatosis. In contrast, Cebpb ΔuORF males on HFD are protected against these metabolic disturbances, which also correlated with better maintenance of glucose tolerance.

We have shown earlier that the expression of genes related to fatty acid oxidation is enhanced in the liver of Cebpb ΔuORF mice accompanied by a significant increase in fatty acid oxidation Zidek et al.

This enhanced fat utilization likely contributes to the reduced lipid accumulation in the liver of Cebpb ΔuORF mice on HFD, and the healthier metabolic phenotype of Cebpb ΔuORF mice is presumably the result of the combination of an increase in WAT function and fat utilization.

In addition, the Cebpb ΔuORF males store relatively more fat in the subcutaneous compartment than wt mice, which relieves the fat storage pressure for the visceral depots. Fat storage in the subcutaneous fat depot is associated with a better metabolic health status in humans and mice, while fat storage in the visceral fat depot is associated with insulin resistance and inflammation Carey et al.

In contrast to the males, female Cebpb ΔuORF mice showed reduced fat accumulation in the subcutaneous fat depot upon HFD compared to wt mice, and the visceral fat depot showed a trend towards a reduced fat storage although this difference was not statistically significant Figure 1F and G.

However, similar to the Cebpb ΔuORF males, the adipocyte cell size in the visceral fat from Cebpb ΔuORF females was significantly reduced and the calculated number of adipocytes was higher compared to wt females revealing increased adipocyte hyperplasia also in HFD fed Cebpb ΔuORF females.

Accordingly, also the female mice showed an improved metabolic phenotype on HFD including reduced hepatic steatosis and better maintained glucose tolerance. The difference in inflammation between wt and Cebpb ΔuORF females was less pronounced compared to males and only visible in antibody staining of the macrophage marker CD68 indicating reduced macrophage infiltration in the visceral fat of Cebpb ΔuORF females.

However, macrophage infiltration seemed to be less pronounced in wt females on HFD than in wt males based on the CD68 immunohistological staining compare Figures 3B and 4B , which might be explained by the known anti-inflammatory function of β-estradiol Camporez et al.

The generally lower vulnerability for inflammation in females may mitigate the differences in inflammatory cytokines between the two genotypes. The HFD induced adipocytic hyperplasia in Cebpb ΔuORF mice indicates that unconstrained LAP functionality — through loss of inhibitory function of LIP — stimulates adipocyte differentiation and function.

It may explain why Cebpb ΔuORF male mice store more fat in WAT on a HFD than wt littermates assuming that efficient fat storage by adaptive increase of the number of adipocytes prevents relocation of fat to peripheral tissues.

Although fat storage in female Cebpb ΔuORF mice upon HFD was rather reduced compared to wt littermates, also their adipocyte numbers in the visceral fat depot were increased. These observations are in line with our previous experiments showing that mouse embryonic fibroblasts MEFs derived from Cebpb ΔuORF mice are much more efficiently induced to undergo adipogenesis than wt MEFs, and differentiation of 3T3-L1 preadipocytes is strongly suppressed upon ectopic induction of LIP see data in Expanded View Figure 3 B, C of Zidek et al.

Pharmacological activation of PPARγ by thiazolidines similarly to the Cebpb ΔuORF mutation stimulates adipocyte differentiation, results in fat storage in hyperplastic adipocytes and in a shift to fat storage in the subcutaneous compartment, resulting in improved metabolic health Adams et al.

This might be an adaptive response to increased LAP function yet does not seem to affect the adipocyte hyperplasia phenotype. Accordingly, the mRNA expression levels of the adipogenic transcription factors are maintained upon HFD feeding in wt females.

Whether this sex-specific difference might be due to the less pronounced inflammation macrophage infiltration observed in females or to other sex-specific responses to HFD feeding has to be examined in future studies. Probably, the slight increase in PPARγ expression together with the increased LAP function might be sufficient for the observed adipocyte hyperplasia in female Cebpb ΔuORF mice on HFD, which however, seems to be less pronounced compared to HFD fed Cebpb ΔuORF males.

The downregulation of fatty acid synthetase FAS mRNA levels that we observe in wt mice upon HFD seems to be independent from the expression of the adipogenic transcription factors tested because at least in females these regulatory events were uncoupled and might be due to other effects of HFD feeding.

Furthermore, in Cebpb ΔuORF females the protein expression of FAS on HFD does not correspond to the FAS mRNA levels, it is efficiently reduced despite almost completely maintained mRNA levels suggesting interfering, post-transcriptional effects.

What these effects are and why they are only observed in female mice is so far not known. Taken together, our data propose pharmacological reduction of LIP expression as an approach to switch the unhealthy metabolic phenotype of obese individuals into a healthy obese phenotype to prevent the development of metabolic disease possibly together with pharmacologic PPARγ activation.

We have shown that a search for such an intervention is feasible through the identification of drugs that inhibit LIP expression similar to mTORC1-inhibition Zaini et al. One drug that we identified as an inhibitor of LIP expression, the antiviral drug adevovir dipivoxil Zaini et al.

Remarkably, adevovir treatment resulted in a significant reduction of body weight and fat content particularly in the HFD fed mice Bitto et al. Furthermore, it will be interesting to examine whether adevovir treatment of males results in reduced fat accumulation like in females or in increased subcutaneous fat accumulation as we observed in the Cebpb ΔuORF males.

Cebpb ΔuORF mice Wethmar et al. For each genotype, weight-matched mice were distributed over the different diet groups. Mice were analyzed at different time points as indicated in the figure legends. The determination of male body weight and food intake per cage divided through the number of mice in the cage was performed weekly for 16 or 18 weeks, respectively.

The body weight of females was determined in week 19 after mice were terminated. During the performance of all experiments the genotype of the mice was masked.

Mice were anesthetized and the abdominal region from lumbar vertebrae 5—6 was analyzed using an Aloka LaTheta Laboratory Computed Tomograph LCTA Zinsser Analytic as described in Zidek et al.

Both the feces and samples of the HFD food were collected, dried in a speed vacuum dryer at 60 °C for 5 hr, grinded and pressed into tablets. The energy content of both the feces and food samples was determined through bomb calorimetry using an IKA-Calorimeter C The energy efficiency was calculated through subtraction of the energy loss in the feces from the energy consumed.

After different time points, the blood glucose concentration was measured using a glucometer AccuCheck Aviva, Roche. injected into non-starved mice using 10 μl per gram body weight and the blood glucose concentration was measured as described above. Adipocyte area was determined using the ImageJ software from 12 adjacent cells per mouse.

For CD68 staining, sections 5 μm from paraffin embedded tissue were dried for 2 hr at 55 °C, deparaffinized and rehydrated. For antigen retrieval, sections were incubated for 25 min in 10 mM citrate buffer, pH 6.

Slides were stained with DAB and counterstained with hematoxylin, dehydrated and covered using Eukitt. A Hamamatsu scanner was used to take images. After shortly washing first with isopropanol and then with water, cells were counterstained with hematoxylin and covered with 10 mM Tris HCl pH 9.

For males, the mean volume of the visceral fat as determined by CT analysis was then divided by the mean adipocyte volume to get the cell number.

For females, adipocyte weight was calculated by multiplying the calculated cell volume with 0. Then, the mean weight of the visceral WAT tissue was divided by the calculated adipocyte weight.

After termination of the mice organs were collected and cleaned from surrounding fat or connective tissue and their weight was determined using an analytical balance.

Tissue pieces were homogenized using the Precellys 24 system Peqlab in the presence of 1 ml QIAzol reagent QUIAGEN. The RNA was isolated using the RNeasy Lipid Tissue Mini kit QUIAGEN according to the protocol of the manufacturer, incubated with RQ1 RNase-free DNase Promega for 30 min at 37 °C and purified further using the RNeasy Plus Mini kit QUIAGEN starting from step 4.

One μg RNA was reverse transcribed into cDNA with Oligo d T primers using the Transcriptor First Strand cDNA Synthesis kit Roche. Tissues were lysed in RIPA buffer as described in Müller et al. Equal amounts of protein were separated by SDS-PAGE and transferred to a PDVF membrane.

For detection, Lightning Plus ECL reagent Perkin Elmer or ECL prime reagent GE Healthcare was used. For re-probing, the membranes were incubated for 15 min with Restore Western Blot Stripping buffer Thermo Fisher. All graphs show average ± standard error of the mean SEM.

Single mice were excluded when results indicated technical failure of the experimental performance. Furthermore, extreme outliers were excluded from the analysis. In the interests of transparency, eLife publishes the most substantive revision requests and the accompanying author responses.

Your article has been reviewed by 2 peer reviewers, and the evaluation has been overseen by a Reviewing Editor and Matt Kaeberlein as the Senior Editor. The reviewers have opted to remain anonymous.

The reviewers have discussed the reviews with one another and the Reviewing Editor has drafted this decision to help you prepare a revised submission.

However, all of the reviewers shared the major concern that it appears that only male mice were studied here, and that this fact — or the rationale for using only male mice — was not clearly articulated within the manuscript. This makes interpretation quite challenging, especially given that the authors previously published that lifespan extension in the uORF KO mice is much more pronounced in female compared to male mice.

There was consensus that this is a substantial weakness to the current manuscript which limits its overall impact. It's possible the authors already have this data, and we would need to see inclusion of data supporting similar outcomes for the key experiments in female mice to recommend publication in eLife.

If the outcomes are different in males and females, this is likely quite interesting and would need to be developed further. The other significant concern was related to the RT-qPCR data, which is indicative but not conclusive support for the authors' conclusions, especially since many of the changes are small in magnitude.

It was noted that most of the relevant proteins have ELISAs available, and they all have antibodies which could be used to support the robustness and importance of the small but plausibly important differences observed.

IHC against CD68 in the fat depots could be performed and the authors could strengthen their claims about adipose tissue inflammation by measuring the expression levels of inflammatory cytokines in adipose depots.

We now included data of female mice complementary to most of the originally performed experiments for males. Bar graphs: in the various figures we now grouped genotypes instead of diet type for — in our opinion — easier assessment.

The body weight of female mice was obtained at the end of the experiment upon termination of the mice Figure 1E. Due to our move to a different institute, we could not perform body composition analysis of females by micro-CT as we did with males and therefore used the weights of visceral and subcutaneous fat obtained from isolated fat tissue from terminated mice at the end of the experiment Figure 1F, G.

We could not include results of food intake and energy efficiency from female mice. Figure 2: panel A shows male data from previous Figure 1E and panel B show new data from females.

Figure 3: Panel A was shown in previous Figure 1F. The panels B and C shows new data for males. IHC against CD68 in the visceral fat depot were performed that strengthen the claim about macrophage infiltration in the visceral adipose tissue B.

In addition, we included qPCR analyses of the inflammatory cytokines TNFα, MCP1, IL-1β an IL-6 in visceral fat from males C. Figure 4: Shows new data from females complementary to the male data in Figure 3.

Also here, qPCR analysis of CD68 expression C , IHC against CD68 B and qPCR analyses of the inflammatory cytokines TNFα, MCP1, IL-1β an IL-6 in the visceral fat depot were performed. Figure 5: Panel A and C show male data previously shown in Figure 2A and figure 2 supplement 1A.

Panels B and D show new data for females. The lipid staining in livers from female was performed using Oil-Red-O Figure 5B instead of Sudan III that was used for males.

Figure 5 supplement 1: Panels A, B and C show male data previously shown in Figure 2 B, C and Figure 2 supplement 1 B. Panel D shows new data from females. Figure 6: Panel A and C show data from males previously shown in Figure 3. Panels B and D show new data from females.

Figure 7: Panel A shows data from males previously shown in Figure 4. Panel B shows data from females. We show immunoblot analysis of genes whose expression was different between the diets as determined by qPCR analysis. Figure 8: shows all new data for males and females.

Discussion: The section has been extended based on added results and suggestions by the reviewers and parts of the discussion on the connection of our findings to the ageing process was removed to limit the extend of this section and to focus more on HFD feeding and obesity. Material and methods: experimental details have been supplemented based on added data.

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. We thank Susanne Klaus and Susanne Keipert DIfE, Potsdam for help with bomb calorimetry and Maaike Oosterveer UMCG for providing the SREBP1 antibody. At the FLI, Verena Kliche for technical assistance, the staff of the animal house facility for embryo transfer and advice on mouse experiments, and Maik Baldauf for help with histology.

This article is distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use and redistribution provided that the original author and source are credited.

Article citation count generated by polling the highest count across the following sources: Crossref , PubMed Central , Scopus. Apicomplexans are ubiquitous intracellular parasites of animals. These parasites use a programmed sequence of secretory events to find, invade, and then re-engineer their host cells to enable parasite growth and proliferation.

The secretory organelles micronemes and rhoptries mediate the first steps of invasion. After invasion, a second secretion programme drives host cell remodelling and occurs from dense granules.

The site s of dense granule exocytosis, however, has been unknown. In Toxoplasma gondii , small subapical annular structures that are embedded in the IMC have been observed, but the role or significance of these apical annuli to plasma membrane function has also been unknown.

Here, we determined that integral membrane proteins of the plasma membrane occur specifically at these apical annular sites, that these proteins include SNARE proteins, and that the apical annuli are sites of vesicle fusion and exocytosis.

Specifically, we show that dense granules require these structures for the secretion of their cargo proteins. When secretion is perturbed at the apical annuli, parasite growth is strongly impaired. The apical annuli, therefore, represent a second type of IMC-embedded structure to the apical complex that is specialised for protein secretion, and reveal that in Toxoplasma there is a physical separation of the processes of pre- and post-invasion secretion that mediate host-parasite interactions.

Cellular metabolism plays an essential role in the regrowth and regeneration of a neuron following physical injury. Yet, our knowledge of the specific metabolic pathways that are beneficial to neuron regeneration remains sparse. Previously, we have shown that modulation of O-linked β-N-acetylglucosamine O-GlcNAc signaling, a ubiquitous post-translational modification that acts as a cellular nutrient sensor, can significantly enhance in vivo neuron regeneration.

Here, we define the specific metabolic pathway by which O-GlcNAc transferase ogt-1 loss of function mediates increased regenerative outgrowth.

Senescent cells accumulate Enhanced metabolic function fat Exercise and blood sugar levels in metabolic syndrome aging. We previously found genetic Enhanced metabolic function Enhancd senescent cells metaholic progeroid INK-ATTAC mice Enhanced metabolic function lipodystrophy. Here we show that Top-rated pre-workout human senescent fat progenitors funcction activin A functiom directly inhibit adipogenesis in non-senescent progenitors. Blocking activin A partially restored lipid accumulation and expression of key adipogenic markers in differentiating progenitors exposed to senescent cells. Mouse fat tissue activin A increased with aging. Clearing senescent cells from month-old naturally-aged INK-ATTAC mice reduced circulating activin A, blunted fat loss, and enhanced adipogenic transcription factor expression within 3 weeks. JAK inhibitor suppressed senescent cell activin A production and blunted senescent cell-mediated inhibition of adipogenesis.

Author: Yonos

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