Identification and characterization of a supraclavicular brown adipose tissue in mice

Mo, Qianxing; Salley, Jordan R.; Roshan, Tony; Baer, Lisa A.; May, Francis J.; Jaehnig, Eric J.; Lehnig, Adam C.; Guo, Xin; Tong, Qiang; Nuotio-Antar, Alli M.; Shamsi, Farnaz; Tseng, Yu‐Hua; Stanford, Kristin I.; Chen, Miao-Hsueh

doi:10.1172/jci.insight.93166

Cited by 34 publications

(39 citation statements)

References 47 publications

(70 reference statements)

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“…It should be noted that laboratory rodents are typically maintained within a highly artificial environment, are usually fed a highly processed diet that is the same each day, experience no change in photoperiod (that is, fixed 12-hour day and 12-hour night) or ambient temperature, and have limited (if any) exposure to pathogens 41 . Furthermore, the main brown (or beige) fat depot in adult humans is located within the supraclavicular region 42 , and although this is also present in rodents 43 , it has seldom been examined, as the interscapular and inguinal depots are primarily investigated.…”

Section: Limitation On Our Understanding Of Regulation Of Brown Fat Mmentioning

confidence: 99%

Recent advances in our understanding of brown and beige adipose tissue: the good fat that keeps you healthy

et al. 2018

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Brown adipose tissue (BAT) possesses a unique uncoupling protein (UCP1) which, when activated, enables the rapid generation of heat and the oxidation of lipids or glucose or both. It is present in small amounts (~15–350 mL) in adult humans. UCP1 is rapidly activated at birth and is essential in preventing hypothermia in newborns, who rapidly generate large amounts of heat through non-shivering thermogenesis. Since the “re-discovery” of BAT in adult humans about 10 years ago, there has been an exceptional amount of research interest. This has been accompanied by the establishment of beige fat, characterised as discrete areas of UCP1-containing cells dispersed within white adipocytes. Typically, the amount of UCP1 in these depots is around 10% of the amount found in classic BAT. The abundance of brown/beige fat is reduced with obesity, and the challenge is to prevent its loss with ageing or to reactivate existing depots or both. This is difficult, as the current gold standard for assessing BAT function in humans measures radio-labelled glucose uptake in the fasted state and is usually dependent on cold exposure and the same subject can be found to exhibit both positive and negative scans with repeated scanning. Rodent studies have identified multiple pathways that may modulate brown/beige fat function, but their direct relevance to humans is constrained, as these studies typically are undertaken in cool-adapted animals. BAT remains a challenging organ to study in humans and is able to swiftly adapt to changes in the thermal environment and thus enable rapid changes in heat production and glucose oxidation.

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Section: Limitation On Our Understanding Of Regulation Of Brown Fat Mmentioning

confidence: 99%

Recent advances in our understanding of brown and beige adipose tissue: the good fat that keeps you healthy

et al. 2018

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“…There are different mechanisms of action of glucagon induced energy expenditure including enhanced activation of brown adipose tissue (BAT) (Billington et al, 1991 ; Kinoshita et al, 2014 ). Uncoupling protein-1 (UCP-1)-positive BAT in adult humans (supraclavicular neck region) and rodents can be activated by a variety of stimuli including cold exposure (Sacks and Symonds, 2013 ; Brychta and Chen, 2017 ; Mo et al, 2017 ). Glucagon knockout mice have reduced thermogenic responses to cold exposure and pharmacological adrenergic stimulation, which is restored by glucagon replacement (Kinoshita et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Involvement of Glucagon in Preventive Effect of Menthol Against High Fat Diet Induced Obesity in Mice

et al. 2018

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Glucagon mediated mechanisms have been shown to play clinically significant role in energy expenditure. The present study was designed to understand whether pharmacological mimicking of cold using menthol (TRPM8 modulator) can induce glucagon-mediated energy expenditure to prevent weight gain and related complications. Acute oral and topical administration of TRPM8 agonists (menthol and icilin) increased serum glucagon concentration which was prevented by pre-treatment with AMTB, a TRPM8 blocker. Chronic administration of menthol (50 and 100 mg/kg/day for 12 weeks) to HFD fed animals prevented weight gain, insulin resistance, adipose tissue hypertrophy and triacylglycerol deposition in liver. These effects were not restricted to oral administration, but also observed upon the topical application of menthol (10% w/v). The metabolic alterations caused by menthol in liver and adipose tissue mirrored the known effects of glucagon, such as increased glycogenolysis and gluconeogenesis in the liver, and enhanced thermogenic activity of white and brown adipose tissue. Correlation analysis suggests a strong correlation between glucagon dependent changes and energy expenditure markers. Interestingly, in-vitro treatment of the serum of menthol treated mice increased energy expenditure markers in mature 3T3L1 adipocytes, which was prevented in the presence of non-competitive glucagon receptor antagonist, L-168,049, indicating that menthol-induced increase in serum glucagon is responsible for increase in energy expenditure phenotype. In conclusion, the present work provides evidence that glucagon plays an important role in the preventive effect of menthol against HFD-induced weight gain and related complications.

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“…Similarly, the removal of iWAT, a depot that “browns” in response to voluntary wheel running, did not blunt the beneficial metabolic effects of exercise training in mice (1). However, it is worth noting that thermogenic supraclavicular BAT has recently been identified in rodents, and its contribution was not accounted for in the current report (45).…”

Section: Discussionmentioning

confidence: 59%

Loss of glucagon signaling alters white adipose tissue browning

et al. 2019

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Various endocrine factors contribute to cold‐induced white adipose tissue (WAT) browning, but glucagon has largely been ignored. The purpose of the current investigation was to determine if glucagon was required for the effects of cold on WAT browning. Utilizing whole‐body glucagon receptor knockout (Gcgr−/−) mice and their wild‐type (WT) littermate controls, we examined the response of inguinal WAT (iWAT) and interscapular brown adipose tissue (BAT) to an acute (48 h) cold stress or challenge with the β3‐adrenergic agonist CL316,243. The effects of glucagon alone on the induction of thermogenic genes in adipose tissue from C57BL6/J mice were also examined. Gcgr−/− mice displayed modest increases in indices of browning at room temperature while displaying a blunted induction of Ucp1, Cidea, and Ffg21 mRNA expression in iWAT following cold exposure. Similarly, cold induced increases in mitochondrial DNA copy number, and the protein content of mitochondrial respiratory chain complexes, UCP1, and PGC1α were attenuated in iWAT from Gcgr−/− mice. In BAT, the induction of thermogenic markers following cold exposure was reduced, but the effect was less pronounced than in iWAT. Glucagon treatment increased the expression of thermogenic genes in both iWAT and BAT of C57BL6/J mice. In response to CL316,243, circulating fatty acids, glycerol, and the phosphorylation of hormone‐sensitive lipase were attenuated in iWAT of Gcgr−/− mice. We provide evidence that glucagon is sufficient for the induction of thermogenic genes in iWAT, and the absence of intact glucagon signaling blunts the cold‐induced browning of WAT, possibly due, in part, to impaired adrenergic signaling.—Townsend, L. K., Medak, K. D., Knuth, C. M., Peppier, W. T., Charron, M. J., Wright, D. C. Loss of glucagon signaling alters white adipose tissue browning. FASEB J. 33, 4824–4835 (2019). http://www.f asebj.org

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Identification and characterization of a supraclavicular brown adipose tissue in mice

Cited by 34 publications

References 47 publications

Recent advances in our understanding of brown and beige adipose tissue: the good fat that keeps you healthy

Recent advances in our understanding of brown and beige adipose tissue: the good fat that keeps you healthy

Involvement of Glucagon in Preventive Effect of Menthol Against High Fat Diet Induced Obesity in Mice

Loss of glucagon signaling alters white adipose tissue browning

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