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Thermogenesis and body composition

Thermogenesis and body composition

Roberto Vettor, Angelo Di Vincenzo, … Marco Rossato. Goldman Thegmogenesis, Buskirk ER Body volume determination by underwater weighing: description of a method. Int J Obes. e —


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Thermogenesis and body composition -

In addition to UCP3-associated uncoupling and thermogenesis, recent data suggest that SERCA-driven beige cell thermogenesis also occurs in pigs.

Indeed, the work by Ikeda et al. Ikeda et al. Retroviral expression of PRDM in subcutaneous porcine adipocytes increases the expression of beige-cell-specific markers including CIDEA and TMEM26 Ikeda et al.

Furthermore, decreased SERCA2b expression reduced basal and noradrenaline-induced oxygen consumption and extracellular acidification rates in isolated pig adipocytes Ikeda et al. Thus, it is now clear that adipose tissue thermogenesis and the associated energy expenditure are not solely mediated via UCP1 and mitochondrial uncoupling, but in fact, a number of cellular pathways, across both adipose tissue and skeletal muscle, act in concert to determine total thermogenic potential.

In lambs, the expression of UCP1 is maximal in perirenal adipose tissue on the first postnatal day, rapidly declining with the expansion of WAT Symonds , Pope et al. Mapping of UCP1 mRNA in lambs shows abundant expression in sternal and retroperitoneal adipose depots compared to omental fat, which is a predominantly WAT depot Symonds et al.

Indeed, adult sheep retain UCP1 expression in both sternal and retroperitoneal fat and this coincides with post-prandial heat production, albeit this response is greater in the sternal fat depot Henry et al.

This coincides with the expression of UCP1 protein, where UCP1-positive brown-like adipocytes were only detectable in sternal adipose tissue of adult ewes Henry et al. Data logger temperature probes have been employed to measure longitudinal heat production in multiple tissues to index thermogenic output in sheep.

Sheep are a grazing species and therefore do not display typical meal-associated excursions such as changes in ghrelin secretion. Despite this, temporal food restriction in sheep entrains a pre-prandial rise in ghrelin Sugino et al.

Furthermore, post-prandial thermogenesis in both skeletal muscle and retroperitoneal adipose depots is markedly enhanced by intracerebroventricular infusion of leptin Henry et al.

Thus, in spite of relatively low levels of UCP1 in adult sheep, skeletal muscle and specific adipose depots retain thermogenic capacity. Over recent years, we have utilised the sheep to dissect the differential roles of adipose tissue and skeletal muscle thermogenesis in the long-term control of body weight, which is discussed in detail in the following section.

Similar to other species, ovine body weight can be readily manipulated through dietary management Henry et al. Sheep are ruminants and thus body weight is increased through feeding a high-energy diet enriched in lupin grain and oats.

Diet-induced obesity, however, is not associated with any change in heat production in adipose tissues or skeletal muscle of sheep Henry et al. On the other hand, long-term food restriction and low body weight are associated with a homeostatic decrease in thermogenesis in sternal and retroperitoneal adipose tissue and skeletal muscle Henry et al.

Importantly, similar to humans, the reduction in thermogenesis caused by food restriction and low body weight is still evident at one year post-weight loss, which suggests that homeostatic changes in thermogenesis contribute to impaired weight loss and increased long-term weight regain Henry et al.

Effect of chronic food restriction and weight loss on adaptive thermogenesis in ewes. Tissue temperature recordings show that caloric restriction and low body weight cause a homeostatic decrease in night time thermogenesis in ovariectomised ewes. This metabolic adaptation occurs in both sternal adipose tissue adipose tissue enriched in uncoupling protein 1 and skeletal muscle and to a lesser extent in retroperitoneal adipose tissue.

The reduction in thermogenesis is associated with increased expression of neuropeptide Y NPY in the arcuate nucleus and melanin-concentrating hormone MCH in the lateral hypothalamus. The homeostatic reduction in thermogenesis is coordinated by the hypothalamus.

Long-term weight loss in ovariectomised ewes increases the expression of the orexigenic neuropeptides NPY in the arcuate nucleus and melanin-concentrating hormone MCH in the lateral hypothalamus LH to increase hunger and reduce energy expenditure Henry et al.

Regarding the anorexigenic melanocortin pathway, the effect of low body weight on the expression of POMC is controversial with data showing a decrease Backholer et al.

This is not surprising since POMC is the precursor to multiple neuropeptides, only one of which includes aMSH and the ultimate end product is dependent on post-translational processing Mountjoy On the other hand, increased Agrp and Npy expression and reduced Pomc mRNA have been observed in rodents Bi et al.

Thus, weight-loss-induced changes in hypothalamic gene expression are likely to reduce thermogenesis, whilst causing a concurrent increase in hunger drive. This represents a homeostatic mechanism to protect against weight loss and promote weight regain in calorie-restricted individuals.

Animals were originally selected for innate differences in adiposity by measuring back fat thickness and two lines were created via selective breeding strategies. A key feature of the genetically lean and obese sheep is an inherent difference in the growth hormone GH axis, where lean animals have increased mean GH concentration in plasma and an associated increase in pituitary gland weight Francis et al.

The increase in pituitary gland weight is primarily due to a greater number of cells in the lean animals Francis et al. Furthermore, expression of GH and the GH secretagogue receptor GHSR is greater in genetically lean sheep, indicating differential responses to ghrelin, an agonist of the GHSR French et al.

This suggests that innate differences in the set-point of the GH axis may underpin differences in adiposity in the genetically lean and obese sheep; however, this is only one aspect that could contribute to this phenotype.

Interestingly, food intake is similar in genetically lean and obese sheep as is the expression of POMC, Leptin Receptor and NPY in the arcuate nucleus.

On the other hand, lean animals have elevated post-prandial thermogenesis in retroperitoneal adipose tissue and this coincides with increased expression of UCP1 in this tissue Henry et al. The divergence in thermogenesis is specific to adipose tissue since post-prandial thermogenesis is similar in genetically lean and obese animals Henry et al.

Despite similar expression of appetite-regulating peptides in the arcuate nucleus of the hypothalamus, genetically lean sheep have increased expression of MCH and pre-pro-orexin ORX in the LH compared to obese animals Anukulkitch et al.

While both neuropeptides are considered orexigenic Shimada et al. Deletion of MCH in mice results in hypophagia and a lean phenotype Shimada et al. Orexin is critical in the embryonic development of BAT in mice Sellayah et al.

Thus, increased expression of ORX in the LH of lean sheep may be an important physiological determinant of increased thermogenesis in retroperitoneal fat and the associated changes in adiposity. It is widely recognised that there is marked variation in the glucocorticoid response to stress or activation of the hypothalamo-pituitary adrenal HPA axis Cockrem , Walker et al.

The activity of the HPA axis in response to stress is impacted on by age Sapolsky et al. Nonetheless, in any given population individuals can be characterised as either high HR or low LR glucocorticoid responders Epel et al.

It is important to note that female LR and HR sheep have similar basal plasma cortisol concentration and divergence in glucocorticoid secretion only occurs in response to ACTH or stress Lee et al. Previous studies have suggested that obesity itself causes perturbation of the HPA axis with impaired glucocorticoid-negative feedback Jessop et al.

Furthermore, cortisol directly impacts on metabolic function; however, this will not be addressed in the current review. Initial studies in rams show that high cortisol response to adrenocorticotropin ACTH is associated with lower feed-conversion efficiency Knott et al. Furthermore, in rams, adiposity is correlated to cortisol responses to ACTH Knott et al.

More recent work shows that identification of high HR and low LR cortisol responders in female sheep can predict altered propensity to gain weight when exposed to a high-energy diet, where HR gain more adipose tissue than LR Lee et al.

Thus, at least in female sheep, data suggest that cortisol responses can be used as a physiological marker that predicts propensity to become obese. Previous studies in women suggest that HR eat more after a stressful episode than LR Epel et al.

Furthermore, HR individuals display preference for foods of high fat and sugar in response to psychological stress Tomiyama et al.

Similarly, in ewes, baseline food intake is similar in LR and HR, but HR eat more following either psychosocial barking dog or immune lipopolysaccharide exposure stressors Lee et al.

In addition to altered food intake, HR ewes have reduced thermogenesis in skeletal muscle only; in response to meal feeding, post-prandial thermogenesis in skeletal muscle is greater in LR than in HR Lee et al. This again exemplifies divergence in the control of adipose tissue and skeletal muscle thermogenesis Fig.

Schematic depiction of the altered metabolic phenotype in animals selected for either high or low cortisol responsiveness. Sheep are characterised as either high HR or low LR cortisol responders when given a standardised dose of adrenocorticotropic hormone.

Animals characterized as HR have increased propensity to become obese, which is associated with perturbed control of food intake and reduced energy expenditure.

Post-prandial thermogenesis in skeletal muscle is decreased in HR compared to LR ewes. Furthermore, food intake in response to stress is greater in HR than in LR and the former are resistant to the satiety effect of alpha-melanocyte stimulating hormone aMSH.

High-cortisol-responding animals have reduced expression of the melanocortin 4 receptor MC4R in the paraventricular nucleus of the hypothalamus PVN.

We propose that the decreased levels of MC4R underpin the altered metabolic phenotype and increased propensity to become obese when compared to LR. For example, at baseline in the non-stressed resting state, HR individuals show an overall upregulation of the HPA axis, with increased expression of CRF and arginine vasopressin, but reduced expression of oxytocin in the PVN Hewagalamulage et al.

In addition to altered expression of genes within the HPA axis, a key neuroendocrine feature of the LR and HR animals is altered expression of the MC3R and MC4R in the PVN Fig.

Reduced MC4R expression coincides with the development of melanocortin resistance. Central infusion of leptin reduces food intake in both LR and HR animals, but intracerebroventricular infusion of aMSH reduces food intake in LR only. Thus, reduced MC4R expression appears to be central to the metabolic phenotype of HR that confers increased propensity to become obese in HR individuals Fig.

Interestingly, gene expression of NPY , AgRP and POMC in the arcuate nucleus is equivalent in LR and HR Hewagalamulage et al. Hence, differences in the control of food intake and thermogenesis are most likely manifest at the level of the melanocortin receptor.

Indeed, previous work in sheep has shown the MC4R to be central in mediating the reduction in food intake caused by immune challenge Sartin et al. Furthermore, in rodents, direct injection of the melanocortin agonist melanotan II into the ventromedial nucleus of the hypothalamus increases skeletal muscle thermogenesis Gavini et al.

We propose that reduced expression of the MC4R in HR animals underpins the metabolic phenotype wherein food intake is relatively increased in response to stress and reduced post-prandial thermogenesis in skeletal muscle is associated with propensity to become obese.

Historically, thermogenesis was considered to primarily occur in brown adipocytes and was solely driven by UCP1. It is now recognised that beige adipocytes and skeletal muscle also contribute to total thermogenic capacity and that thermogenesis is differentially regulated in these tissues. Indeed, in beige adipocytes, thermogenesis occurs via three distinct mechanisms, with these being UCP1-driven mitochondrial uncoupling, futile creatine cycling and futile calcium cycling.

On the other hand, in skeletal muscle, thermogenesis is associated with UCP3 and futile calcium cycling. Unlike rodents, large mammals including sheep and pigs do not contain a defined or circumscribed brown fat depot but have dispersed brown adipocytes within traditionally white fat depots.

Large animals have provided invaluable insight into alternative mechanisms of thermogenesis. The sheep has been particularly useful in delineating the differential role of adipose tissue and skeletal muscle in the control of body weight.

Furthermore, sheep models have allowed characterisation of the neuroendocrine pathways that may contribute to altered thermogenesis. We have shown that in sheep, both skeletal muscle and BAT differentially contribute to thermogenesis and therefore total energy expenditure. Changes in thermogenesis, however, do not exclusively associate with altered gene expression at the level of the arcuate nucleus.

Indeed, decreased MC4R expression in HR animals and reduced orexin expression in the genetically obese animals coincide with altered thermogenic output. This review highlights the importance of the use of large animal models to ascertain the contribution and control of thermogenesis in multiple tissues and the relative role in the regulation of body weight.

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this review. This work was supported by Australian Research Council grant number DP and National Health and Medical Research Council grant number APP Animal Science 63 — Journal of Pathology and Bacteriology 91 — Obesity Reviews 19 — Molecular Metabolism 5 — Neuroendocrinology 91 — Biochimica et Biophysica Acta — Astrup A Thermogenesis in human brown adipose tissue and skeletal muscle induced by sympathomimetic stimulation.

Acta Endocrinologica Supplement S9 — S American Journal of Physiology E — E Science — Neuroendocrinology 91 27 — Journal of Biological Chemistry — Bal NC , Maurya SK , Sopariwala DH , Sahoo SK , Gupta SC , Shaikh SA , Pant M , Rowland LA , Bombardier E , Goonasekera SA , et al.

Nature Medicine 18 — Journal of Neuroendocrinology 29 e Balthasar N , Dalgaard LT , Lee CE , Yu J , Funahashi H , Williams T , Ferreira M , Tang V , McGovern RA , Kenny CD , et al. Cell — American Journal of Physiology R — R Banks WA Characteristics of compounds that cross the blood-brain barrier.

BMC Neurology 9 S3 — S3. American Journal of Physiology: Endocrinology and Metabolism E — E Disease Models and Mechanisms 9 — Cellular and Molecular Life Sciences 73 — PLoS Genetics 2 e Cell Metabolism 25 e — Lancet — Circulation Research — American Journal of Physiology: Regulatory, Integrative and Comparative Physiology R — R International Journal of Obesity and Related Metabolic Disorders 17 Supplement 3 S78 — S Blondin DP , Daoud A , Taylor T , Tingelstad HC , Bezaire V , Richard D , Carpentier AC , Taylor AW , Harper ME , Aguer C , et al.

Journal of Physiology — International Journal of Obesity 37 — PLoS ONE 11 e Progress in Neuro-Psychopharmacology and Biological Psychiatry 35 — Metabolism 64 — Physiology Reviews 84 — Carey AL , Pajtak R , Formosa MF , Van Every B , Bertovic DA , Anderson MJ , Eikelis N , Lambert GW , Kalff V , Duffy SJ , et al.

Diabetologia 58 — Endocrinology — Cinti S The adipose organ: morphological perspectives of adipose tissues. Proceedings of the Nutrition Society 60 — Claret M , Smith MA , Batterham RL , Selman C , Choudhury AI , Fryer LG , Clements M , Al-Qassab H , Heffron H , Xu AW , et al.

Journal of Clinical Investigation — Clement K , Vaisse C , Lahlou N , Cabrol S , Pelloux V , Cassuto D , Gourmelen M , Dina C , Chambaz J , Lacorte JM , et al. Nature — Cockrem JF Individual variation in glucocorticoid stress responses in animals. General and Comparative Endocrinology 45 — Diabetes 64 — Coppola A , Liu Z , Andrews Z , Paradis E , Roy M-C , Friedman JM , Ricquier D , Richard D , Horvath TL , Gao X-B , et al.

Cell Metabolism 5 21 — Journal of Cell Science — Neuron 24 — Clinical Science 69 — Cypess AM , Lehman S , Williams G , Tal I , Rodman D , Goldfine AB , Kuo FC , Palmer EL , Tseng Y-H , Doria A , et al.

New England Journal of Medicine — Cypess AM , Weiner LS , Roberts-Toler C , Elia EF , Kessler SH , Kahn PA , English J , Chatman K , Trauger SA , Doria A , et al. Cell Metabolism 21 33 — Nature Medicine 19 — Dalgaard K , Landgraf K , Heyne S , Lempradl A , Longinotto J , Gossens K , Ruf M , Orthofer M , Strogantsev R , Selvaraj M , et al.

Bioscience Reports 25 — Neuron 23 — Psychoneuroendocrinology 26 37 — Farooqi IS Monogenic human obesity. Frontiers of Hormone Research 36 1 — New Zealand Journal of Agricultural Research 41 — Domestic Animal Endocrinology 18 — Journal of Animal Science 84 — American Journal of Physiology: Physiological Genomics 38 54 — Gaborit B , Venteclef N , Ancel P , Pelloux V , Gariboldi V , Leprince P , Amour J , Hatem SN , Jouve E , Dutour A , et al.

Cardiovascular Research 62 — Diabetes, Obesity and Metabolism 16 97 — Hara J , Beuckmann CT , Nambu T , Willie JT , Chemelli RM , Sinton CM , Sugiyama F , Yagami K , Goto K , Yanagisawa M , et al.

Neuron 30 — Heaton JM The distribution of brown adipose tissue in the human. Journal of Anatomy 35 — Journal of Animal Science 93 — Journal of Chemical Neuroanatomy 13 1 — Neuroendocrinology 27 44 — Clinical Pediatrics 49 — American Journal of Physiology: Cell Physiology C Biochemical and Biophysical Research Communications — Ikeda K , Kang Q , Yoneshiro T , Camporez JP , Maki H , Homma M , Shinoda K , Chen Y , Lu X , Maretich P , et al.

Neuroscience — Ito M , Gomori A , Ishihara A , Oda Z , Mashiko S , Matsushita H , Yumoto M , Ito M , Sano H , Tokita S , et al. Nature Genetics 16 Jespersen NZ , Larsen TJ , Peijs L , Daugaard S , Homoe P , Loft A , de Jong J , Mathur N , Cannon B , Nedergaard J , et al. Cell Metabolism 17 — Journal of Clinical Endocrinology and Metabolism 86 — Journal of the American College of Nutrition 21 55 — Diabetes 50 — British Journal of Pharmacology — Kazak L , Chouchani Edward T , Jedrychowski Mark P , Erickson Brian K , Shinoda K , Cohen P , Vetrivelan R , Lu Gina Z , Laznik-Bogoslavski D , Hasenfuss Sebastian C , et al.

Handbook of Experimental Pharmacology — Domestic Animal Endocrinology 34 — Nature Genetics 19 — International Journal of Obesity 38 — FASEB Journal 28 35 — Psychoneuroendocrinology 47 — Experimental and Clinical Endocrinology and Diabetes Supplement 1 S4 — S6.

International Journal of Obesity 35 Journal of Molecular Cell Biology 9 — Locke AE , Kahali B , Berndt SI , Justice AE , Pers TH , Day FR , Powell C , Vedantam S , Buchkovich ML , Yang J , et al. Lopez M , Varela L , Vazquez MJ , Rodriguez-Cuenca S , Gonzalez CR , Velagapudi VR , Morgan DA , Schoenmakers E , Agassandian K , Lage R , et al.

Nature Medicine 16 — In Current Protocols in Pharmacology , chapter 5, unit 5. Hoboken, NJ, USA : Wiley. Metabolism 41 — UCP2 or UCP3 do not substitute for UCP1 in adrenergically or fatty acid-induced thermogenesis. Biology of Reproduction 49 — Temperature 3 — Montague CT , Farooqi IS , Whitehead JP , Soos MA , Rau H , Wareham NJ , Sewter CP , Digby JE , Mohammed SN , Hurst JA , et al.

Animal Science 65 93 — Morrison SF Central neural control of thermoregulation and brown adipose tissue. Autonomic Neuroscience: Basic and Clinical 14 — International Journal of Obesity and Related Metabolic Disorders 19 — Mountjoy KG Functions for pro-opiomelanocortin-derived peptides in obesity and diabetes.

Biochemical Journal — It depends where you look. Psychoneuroendocrinology 32 — Molecular Endocrinology 15 — Metabolism: Clinical and Experimental 64 24 — Journal of Clinical Endocrinology and Metabolism 77 — Obesity Research 13 — Acta Physiologica 20 — American Journal of Clinical Nutrition 88 — Nature Cell Biology 15 — Journal of Clinical Endocrinology and Metabolism 83 — Neonatology 17 53 — Journal of Neuroscience 35 — Saito M , Okamatsu-Ogura Y , Matsushita M , Watanabe K , Yoneshiro T , Nio-Kobayashi J , Iwanaga T , Miyagawa M , Kameya T , Nakada K , et al.

Diabetes 58 — Cell Metabolism 16 — Neurobiology of Aging 7 — Endocrine Reviews 7 — Journal of Animal Science 86 — Reprints and permissions.

Dulloo, A. An adipose-specific control of thermogenesis in body weight regulation. Int J Obes 25 Suppl 5 , S22—S29 Download citation.

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Access through your institution. Buy or subscribe. Change institution. Learn more. Author information Authors and Affiliations Department of Medicine, Institute of Physiology, University of Fribourg, Fribourg, Switzerland AG Dulloo Computer Unit, Faculty of Medicine, University of Geneva, Geneva, Switzerland J Jacquet Authors AG Dulloo View author publications.

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Metabolic adaptation to weight changes relates to body weight control, Innovative athletic supplements and Thermogenesis and body composition. Adaptive thermogenesis Compositlon refers to changes in resting and non-resting Thermogenesis and body composition bkdy REE bodyy nREE which are independent from changes in fat-free mass FFM and FFM composition. AT differs in response to changes in energy balance. With negative energy balance, AT is directed towards energy sparing. It relates to a reset of biological defence of body weight and mainly refers to REE. After weight loss, AT of nREE adds to weight maintenance. Thermogenesis and body composition Thank you Thermogenesis and body composition visiting nature. You are Thermogenesls a browser version composktion limited support for CSS. To obtain Endurance-enhancing supplements best experience, we bpdy you use a more up to date compositiion or turn off Cojposition mode in Internet Composifion. In the Thermogenesis and body composition, to ensure continued support, we are displaying the site without styles and JavaScript. By applying a system-analysis approach in evaluating data on the energetics of starvation and refeeding, evidence is presented here in support of the hypothesis that there are in fact two distinct control systems underlying adaptive thermogenesis. The other is independent of the functional state of the SNS and is dictated solely by signals arising from the state of depletion of the adipose tissue fat stores; it is hence referred to as the adipose-specific control of thermogenesis, and is postulated to occur primarily in the skeletal muscle.

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