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Caloric restriction and insulin sensitivity

caloric restriction and insulin sensitivity

Am J Physiol Endocrinol Metab 5 :E—E Article CAS Caloric restriction and insulin sensitivity Scholar Anx KJ, Sensjtivity A, Nguyen V, Brosnahan J, Lowndes Ca,oric, Angelopoulos TJ, Rippe JM Body composition, Premium seed options caloric restriction and insulin sensitivity, and components of metabolic syndrome in overweight and obese adults after a week trial on dietary treatments focused on portion control, energy density, or glycemic index. The adult, obese U. View raw image Insulin tolerance test ITT in the four experimental groups following 20 weeks of ad libitum or restricted CR feeding. X Twitter Facebook LinkedIn.

Caloric restriction and insulin sensitivity -

Participants were provided with all food for the first 12 weeks and for weeks 22— For weeks 13—22, participants self-selected their diet based on their calorie targets. CREX participants increased their energy expenditure by Participants were required to conduct three sessions per week under supervision.

For unsupervised sessions, participants wore a portable heart rate monitor Polar S, Polar Beat, Port Washington, NY with heart rate and exercise duration recorded. For support, all participants attended weekly group meetings that were led by clinical psychology professionals. All metabolic tests were performed during inpatient stays at baseline and month 6 following a h overnight fast and at least 48 h after the last bout of exercise.

Body fat was measured by dual-energy X-ray absorptiometry QDA A; Hologics, Bedford, MA and multislice computed tomography scanning of the abdominal region GE High Speed Plus; General Electric, Fairfield, CT was performed to quantify abdominal fat compartments Muscle and liver lipid stores were determined by proton magnetic resonance spectroscopy using point-resolved spectroscopy Subcutaneous abdominal needle biopsies were performed, and FCS was determined by the Multisizer-3 counter Beckman Coulter, Fullerton, CA as previously described Insulin sensitivity was determined by the insulin-modified frequently sampled intravenous glucose tolerance test 22 , At 20 min, a bolus injection of insulin 0.

The S i and acute insulin response to glucose AIR g were calculated by the minimal model Because of illness or problems with intravenous lines, four tests could not be analyzed at month 6. Glucose was analyzed using a Synchron CX7 Beckman-Coulter, Brea, CA and insulin was analyzed via immunoassay on the DPC Diagnostic Product Corporation, Los Angeles, CA.

SAS version 9. Pearson or Spearman rank order correlations were used where appropriate, and general linear regression was used to identify any interactions of the changes with sex. To assess the effect of the intervention among the four groups, the change from baseline to month 6 was computed, and an ANCOVA was performed with baseline values included in the model as covariates and adjusted with respect to Tukey-Kramer.

Two subjects withdrew during the study; one was a control subject who withdrew for personal reasons and the other subject, who was following the LCD diet, was lost to follow-up. Data are therefore presented on 46 subjects.

Characteristics of the subjects at baseline are reported in Table 1. Subjects were generally in good health with fasting glucose, insulin, and blood pressure within recommended ranges; 30 Caucasians, 15 African Americans, and 1 Asian were examined. IMCL in the soleus was not correlated with FCS, VAT, or IHL.

All of the above correlations were also statistically significant at month 6 data not shown. The impact of the intervention can be seen in Table 1 by comparing results at month 6 versus baseline. The changes in body composition and abdominal fat were not dependent on whether the caloric deficit was achieved by exercise and diet CREX or diet alone CR and LCD.

The improvement in S i was not different among the three intervention groups. The changes in IMCL, IHL, FCS, and the other abdominal fat depots were not additional independent determinants. These correlation analyses were repeated with the control group removed. The significance of the relationship between the changes in FCS and VAT and the changes in IHL and percent fat was lost, but no other relationships were affected.

In this study we examined the relationships between S i and various indexes of body fat in overweight, glucose-tolerant subjects before and after calorie restriction. At baseline, we found that 1 fat deposition in liver was related to the accumulation of fat in the abdominal visceral area and to enlarged subcutaneous abdominal adipocytes and 2 increased FCS but not ectopic fat deposition in muscle and liver was independently associated with reduced insulin sensitivity.

In response to 6 months of calorie restriction, we found that 1 weight, visceral fat, and FCS are reduced with improvements in S i and reduced AIR g and 2 fat deposition in liver but not muscle was reduced by the intervention, but the changes were not associated with improvements in S i.

Several studies have suggested that ectopic fat accumulation is independent of whole-body adiposity 16 , 24 — However, other studies have noted that lipid accumulation in both muscle 27 , 31 — 33 and liver 34 — 37 increases as a function of obesity, providing that subjects with a wide range of adiposity are studied.

In this study, we observed that lipid deposition in liver but not muscle was related to both total and abdominal adiposity. Specifically, our findings indicate that ectopic fat in the liver may be related to visceral fat stores.

This relationship between liver lipid and visceral adiposity has been noted in some 34 , 38 but not all 29 , 30 studies. Most interestingly, we observed that liver lipid infiltration tended to be greater in overweight individuals who had enlarged adipocytes and increased visceral abdominal adiposity.

Furthermore, visceral fat was related to FCS. These findings support the hypothesis that inadequate subcutaneous adipose stores result in lipid overflow into visceral fat and other nonadipose tissues In this regard, visceral fat could be considered as a marker of ectopic fat.

At baseline and at month 6, large fat cells were also the strongest determinant of insulin resistance in these nondiabetic subjects. This finding prompts speculation that impaired adipogenesis may be the primary defect in insulin resistance, and the hypothesis is supported by findings that humans with partial or complete loss of adipose tissue are extremely insulin resistant 40 , that surgical replacement of adipose stores in the fatless mouse restores insulin sensitivity 41 , and that expression of Wnt signaling genes and adipogenic transcription factors are reduced in nondiabetic subjects with a family history of type 2 diabetes Large fat cells have also been shown to have a different pattern of adipocytokine secretion than smaller fat cells 43 , which may contribute to the strong association between large FCS and insulin sensitivity.

In contrast to previous studies 24 , 26 — 28 , 31 , 44 , 45 , we observed that IMCL was not related to insulin sensitivity. Furthermore, IMCL was not related to adipocyte size. Our results are consistent with the hypothesis that IMCL stores alone are not sufficient to account for impaired insulin action 46 — Liver lipid, on the other hand, was inversely related to insulin sensitivity.

Liver lipid content has previously been reported to correlate with measures of whole-body insulin sensitivity in individuals with and without diabetes 30 , 34 , 35 , 38 , 49 , but this relationship is difficult to explain mechanistically because most ingested or infused glucose is taken up by muscle.

Theoretically, IHL is expected to correlate with reduced hepatic insulin sensitivity impaired insulin suppression of glucose rate of appearance and not necessarily with whole-body insulin action. However, the accumulation of hepatic triglyceride has been hypothesized to reduce insulin clearance and lead to peripheral insulin resistance via a downregulation of insulin receptors 34 , Clearly, prospective human studies that define whether lipid accumulation in liver precedes insulin resistance would be of interest.

Contrary to some previous studies 51 , 52 , we observed that diet alone or with exercise produced identical reductions in weight, fat mass, and abdominal fat mass. These conflicting results may be due to inaccurate calculations of the energy costs of the prescribed activity in those studies, which would lead to differences in energy deficits among groups.

We also observed that FCS was reduced in response to an energy deficit, but we could not detect an additional effect of exercise. Our study was underpowered to detect differences in FCS among groups and our results contrast with the reports of You et al. The current study is also the first to simultaneously measure ectopic fat stores in both muscle and liver in response to a calorie restriction intervention.

We found that the calorie restriction alone or with exercise did not affect IMCL in the soleus. These results are consistent with previous studies 6 , 14 , 15 and together with the findings that IMCL was not independently related to S i suggest that IMCL accumulation alone is not likely to be a causal factor leading to acquired insulin-signaling defects in muscle.

Many other factors, including lipid droplet size, location of lipid droplets relative to mitochondria, and muscle oxidative capacity, are all potential determinants of insulin resistance 15 , 48 , An alternate hypothesis is that the capacity for lipid metabolism is an important mediator in the association between IMCL and insulin resistance.

Caution must be exercised when interpreting these results because the study may have been underpowered to detect small differences in IHL among groups. The reduction in liver lipid levels is consistent with results of Tiikkainen et al. In addition, we also observed parallel reductions in IHL and abdominal visceral fat.

In summary, calorie restriction by diet alone or in conjunction with exercise leads to similar improvements in insulin sensitivity and reductions in β-cell sensitivity in overweight, glucose-tolerant subjects.

The study also provides support for the hypothesis that the underlying pathologic cause of insulin resistance is related to abnormal partitioning of fat among adipose, hepatic, muscle, and pancreatic tissues, probably as a result of an inability to make new fat cells.

However, the finding that IMCL was not responsive to weight loss despite improvements in insulin sensitivity suggests that intracellular fat accumulation is not a causal factor in insulin resistance in muscle. Overall, this study provides new evidence to suggest that impaired adipogenesis and increased liver lipid infiltration occur early in the pathogenesis of insulin resistance.

In healthy overweight men and women at baseline, there was a strong positive correlation between abdominal subcutaneous FCS and VAT A and abdominal subcutaneous FCS and IHL B. Groups were pooled for analysis. The improvement in insulin sensitivity with 6 months of calorie restriction was significantly associated with the loss of fat mass A and abdominal VAT depots B but not to the change in subcutaneous abdominal FCS C and IHL D.

Analyses are reported with and without the control group included. Physical characteristics of the subject groups at baseline and following 6 months of calorie restriction. Differences between treatment groups for the change scores using an ANCOVA with the absolute change as the dependent variable and the baseline score as a covariate.

This work was supported by grants U01 AG to E. and K01 DK to D. is supported by a Neil Hamilton-Fairley Training Fellowship awarded by the National Health and Medical Research Council of Australia ID The authors thank the remaining members of the Pennington CALERIE Research Team: James DeLany, Corby Martin, Julia Volaufova, Marlene Most, Lilian de Jonge, Tuong Nguyen, Frank Greenway, Emily York-Crow, Catherine Champagne, Brenda Dahmer, Andy Deutsch, Paula Geiselman, Jennifer Howard, Jana Ihrig, Michael Lefevre, Darlene Marquis, Connie Murla, Sabrina Yang, Robbie Durand, Sean Owens, Aimee Stewart, and Vanessa Tarver.

Our gratitude is extended to the excellent staffs of the Inpatient Clinic and Metabolic Kitchen. Our thanks also go to Health and Nutrition Technology Carmel, CA for providing us with all of the HealthOne formula used in the study and to Edward J.

Robarge for technical assistance with collection of the magnetic resonance spectroscopy data. Finally, our profound gratitude goes to all the volunteers who spent so much time participating in this very demanding research study.

is currently affiliated with the Department of Family and Consumer Sciences, University of Wyoming, Laramie, Wyoming. Insulin secretion rates from those tests were compared against a glycemia-matched glucose infusion. To measure energy intake, participants completed 3-day food diaries with computerized nutrient analysis.

Insulin sensitivity increased twofold in the group that combined calorie restriction with exercise 2. the calorie restriction-only group 0.

Weight loss was similar across all groups and GIP concentrations decreased in all groups. Participants who combined calorie restriction with exercise performed less exercise and restricted their calories less to ensure similar weight loss across all three groups, according to researchers.

The independent contributions of exercise and calorie intake must be better understood, and future studies that target individuals with prediabetes are warranted, according to researchers.

Disclosure: The researchers report no relevant financial disclosures. Healio News Endocrinology Obesity. April 24, This article is more than 5 years old. Information may no longer be current.

VP carried out adipose tissue gene expression analysis and validation. BH and EV contributed to dietary data analysis. M-ED, JC, and LH carried out the serum and urine metabolomics analysis. FI, EP-G, and CJ carried out the fecal metabolomics analysis.

EP, JD, and J-DZ conducted the microbial data analysis. All authors contributed to the preparation, writing, and approval of the manuscript. The clinical work received support from KOT-Ceprodi, Danone Nutricia Research and the Foundation Coeur et Artère. LH was in receipt of an MRC Intermediate Research Fellowship in Data Science Grant No.

The remaining 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. We thank the subjects for their participation in this study.

We also thank Christine Baudoin who contributed to the clinical investigation study, Soraya Fellahi and Jean-Philippe Bastard Department of Biochemistry and Hormonology, Tenon hospital for analyses of biological markers, Dominique Bonnefont-Rousselot and Randa Bittar Department of Metabolic Biochemistry, Pitié-Salpêtrière Hospital for help with the analysis of plasma lipid profile.

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Caloric restriction has restrictio been shown to caloric restriction and insulin sensitivity insulin action and glucose control. In this chapter, we review the evidence behind different strategies to insuoin calories, its impact Body composition analysis insulin sensitivity, putative mechanisms by inssulin it improves insulin sensitivity, and the longevity restrjction these methods in caloric restriction and insulin sensitivity glucose metabolism where such evidence exists. Coverage includes sections on caloric restriction versus weight loss, techniques, macronutrients, the role of the liver and skeletal muscle after caloric restriction, and the gut microbiome. This is a preview of subscription content, log in via an institution. Amar J, Chabo C, Waget A, Klopp P, Vachoux C, Bermudez-Humaran LG, Smirnova N, Berge M, Sulpice T, Lahtinen S, Ouwehand A, Langella P, Rautonen N, Sansonetti PJ, Burcelin R a Intestinal mucosal adherence and translocation of commensal bacteria at the early onset of type 2 diabetes: molecular mechanisms and probiotic treatment. Calorie restriction CR andd obesity-related insulin resistance restrictoin undefined molecular mechanisms. CR rsetriction obese rats significantly reduced body weight and increased insulin sensitivity compared to AL controls. Concomitantly, obesity increased and Nootropic for ADHD decreased caloric restriction and insulin sensitivity activity of hepatic ERK and p70 S6K against IRS1. The close association between the activity of hepatic ERK and p70 S6K with insulin resistance suggests an important role for ERK and p70 S6K in the development of insulin resistance, presumably via phosphorylation of IRS proteins. Calorie restriction CR may improve the outcome of obesity-associated diseases, including diabetes and cardiovascular disease. At the whole-body level, CR has been shown to reduce visceral fat Barzilai et al.

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