Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity.

Guerra, Carmen; Koza, Robert A.; Yamashita, Hitoshi; Walsh, K.V.; Kozak, Leslie P.

doi:10.1172/jci3155

Cited by 583 publications

(568 citation statements)

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“…18 The retroperitoneal and inguinal fat pads (but not epididymal fat pads to our knowledge) showed emergence of brown fat (in response to cold or b 3 -stimulation) in several previous studies. 22,45,53 Some of these studies indicated that the capacity for brown fat adipogenesis in WAT depends largely on genetic Figure S5). A full color version of this figure is available at the Hypertension Research journal online.…”

Section: Discussionmentioning

confidence: 99%

“…22,53 To understand which specific genes and whether they primarily control fat pad-specific cell-autonomous or whole-tissue properties requires further research, however. Additional studies are also needed to examine whether similar brown fat adipogenesis occurs in other fat depots, including subcutaneous white fat and interscapular brown fat.…”

Section: Discussionmentioning

confidence: 99%

“…PGC-1a regulates mitochondrial biogenesis and fat oxidation by coordinating expression of both mitochondrial genome-and nuclear genome-encoded genes involved in these processes, and it also induces expression of the brown fat-defining UCP1. 19 Previous research suggests that (i) brown fat emergence in WAT can be induced by sympathetic b-adrenergic stimulation [20][21][22] and (ii) dietary fat can increase sympathetic outflow from the central nervous system to the periphery. 23 Given these observations, we hypothesized that the spontaneously hypertensive rat (SHR) may be a genetic strain that is susceptible to the emergence of brown fat in WAT in response to a high-fat diet (HFD), as it is characterized by high sympathetic outflow to the periphery, including to WAT, [24][25][26][27] and shows augmentations in sympathetic activity (indicated indirectly by an augmentation in heart rate) 28 and expression of genes involved in fat burning in WAT in response to a chronic HFD.…”

Section: Introductionmentioning

confidence: 99%

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High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

et al. 2011

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Obesity has a profound adverse impact on health. In this study, we present evidence for high-fat diet (HFD)-induced emergence of brown-like adipocytes in white adipose tissue (WAT) of the spontaneously hypertensive rat (SHR). We studied adult males fed a HFD or normal diet (ND) for 12 weeks. At the end of the 12-week dietary intervention, HFD compared with ND rats showed significantly higher whole-body energy expenditure. HFD vs. ND rats also showed higher expression of genes involved in fatty acid oxidation, mitochondrial biogenesis and brown fat adipogenesis, as well as augmented mitochondrial mass in WAT but not in the liver or skeletal muscle. Consistent with the molecular changes, in HFD but not in ND rats, histological and immunohistochemistry-based analyses of WAT demonstrated the presence of small multilocular cells staining positively for uncoupling protein 1, indicating the emergence of brown-like adipocytes in WAT. Our results suggest that SHR may have the capacity to increase energy expenditure in response to a chronic HFD that may be linked to the emergence of brown-like adipocytes in WAT. Thus, the SHR may be an important genetic model to uncover novel mechanisms of resistance to dietary obesity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

et al. 2011

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“…UCP-1 is specifically produced in BAT; this protein uncouples oxidative phosphorylation from electron transport, resulting in the dissipation of energy as heat [24,25]. The emergence of these ectopic cells in the WAT of rats [26] and of mice [27] was found to be induced by cold acclimatisation or by the administration of selective β3-AR agonists [27,28]. Interestingly, the emergence of brown fat cells in white fat depots was associated with a lean phenotype in several transgenic mouse models, including β1-AR transgenic mice [22], FOXC2 transgenic mice [29] and Tif2 −/− (also known as Ncoa2 −/− ) mice [30].…”

Section: Introductionmentioning

confidence: 99%

Increased fat:carbohydrate oxidation ratio in Il1ra −/− mice on a high-fat diet is associated with increased sympathetic tone

et al. 2008

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Aims/hypothesis Proinflammatory cytokines, including IL-1, exert pleiotropic effects on the neuro-immuno-endocrine system. Previously, we showed that mice with knockout of the gene encoding IL-1 receptor antagonist (Il1ra −/− , also known as Il1rn −/− ) have a lean phenotype. The present study was designed to analyse the mechanisms leading to this lean phenotype.Methods Il1ra −/− mice were fed a high-fat diet following weaning. Energy expenditure, body temperature, heart rate, blood parameters, urinary catecholamines and adipose tissue were analysed. Results Il1ra −/− mice exhibited resistance to obesity induced by a high-fat diet; this resistance was associated with increased energy expenditure and a decreased respiratory quotient, indicating that the ratio of fat:carbohydrate metabolism in Il1ra −/− mice is greater than in controls. Activity level in Il1ra −/− mice was significantly decreased and body temperature was significantly increased, compared with wild-type (WT) mice. Inguinal white adipose tissues in Il1ra −/− mice express increased levels of Ucp1 and mitochondrial respiratory chain genes compared with WT mice. Histological analysis of adipose tissue in Il1ra −/− mice revealed that brown adipose tissue is hyperactive and inguinal white adipose tissue contains smaller cells, which exhibit the distinctive multilocular appearance of brown adipocytes. Urinary epinephrine and norepinephrine excretion in Il1ra −/− mice was significantly increased compared with WT mice, suggesting that Il1ra −/− mice have increased sympathetic tone. Consistent with this, heart rate in Il1ra −/− mice was also significantly increased. Conclusions/interpretation Our results show that Il1ra −/− mice have increased energy expenditure, fat:carbohydrate oxidation ratio, body temperature, heart rate and catecholamine production. All of these observations are consistent with an enhanced sympathetic tone.

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“…Indeed, when studied under the conditions of the above treatments, AMPK in WAT and other tissues was found to be activated (Jelenik et al 2010;Kopecky et al 2009;Orci et al 2004;Ye et al 2006). Concerning the mechanism of energy expenditure induced by the treatments, mitochondrial uncoupling mediated by UCP1 in WAT adipocytes (Orci et al 2004;Tiraby et al 2003;Petrovic et al 2010;Collins et al 1997;Guerra et al 1998;Himms-Hagen et al 2000) could be involved in most of the cases. Further studies are required to learn more about the mechanisms underlying the induction of energy dissipating adipocytes in response to treatments inducing UCP1 in adipose tissue.…”

Section: Treatments Enhancing Energy Expenditurementioning

confidence: 97%

Augmenting energy expenditure by mitochondrial uncoupling: a role of AMP-activated protein kinase

et al. 2011

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Strategies to prevent and treat obesity aim to decrease energy intake and/or increase energy expenditure. Regarding the increase of energy expenditure, two key intracellular targets may be considered (1) mitochondrial oxidative phosphorylation, the major site of ATP production, and (2) AMP-activated protein kinase (AMPK), the master regulator of cellular energy homeostasis. Experiments performed mainly in transgenic mice revealed a possibility to ameliorate obesity and associated disorders by mitochondrial uncoupling in metabolically relevant tissues, especially in white adipose tissue (WAT), skeletal muscle (SM), and liver. Thus, ectopic expression of brown fat-specific mitochondrial uncoupling protein 1 (UCP1) elicited major metabolic effects both at the cellular/tissue level and at the whole-body level. In addition to expected increases in energy expenditure, surprisingly complex phenotypic effects were detected. The consequences of mitochondrial uncoupling in WAT and SM are not identical, showing robust and stable obesity resistance accompanied by improvement of lipid metabolism in the case of ectopic UCP1 in WAT, while preservation of insulin sensitivity in the context of high-fat feeding represents the major outcome of muscle UCP1 expression. These complex responses could be largely explained by tissue-specific activation of AMPK, triggered by a depression of cellular energy charge. Experimental data support the idea that (1) while being always activated in response to mitochondrial uncoupling and compromised intracellular energy status in general, AMPK could augment energy expenditure and mediate local as well as whole-body effects; and (2) activation of AMPK alone does not lead to induction of energy expenditure and weight reduction.

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Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity.

Cited by 583 publications

References 45 publications

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

Increased fat:carbohydrate oxidation ratio in Il1ra −/− mice on a high-fat diet is associated with increased sympathetic tone

Augmenting energy expenditure by mitochondrial uncoupling: a role of AMP-activated protein kinase

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