Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat

Cypess, Aaron M.; White, A.; Vernochet, Cécile; Schulz, Tim J.; Xue, Ruidan; Sass, Christina A.; Huang, Tian Liang; Roberts-Toler, Carla; Weiner, Lorin; Sze, Cathy; Chacko, Aron T.; Deschamps, Laura N.; Herder, Lindsay; Truchan, Nathan A.; Glasgow, Allison L; Holman, Ashley R.; Gavrila, Alina; Hasselgren, Per-Olof J.; Mori, Marcelo A.; Molla, Michael; Tseng, Yu–Hua

doi:10.1038/nm.3112

Cited by 607 publications

(594 citation statements)

References 37 publications

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“…By contrast, Jesperson et al 37 found that tissue and in vitro-differentiated adipocytes from this depot express both brownand beige-specific markers. A different depot in the neck region was shown to have the molecular characteristics of mouse brown fat 38 . Typing these depots as brown or beige on the basis of their expression levels of a few mouse marker genes that have no known function(s) has not been conclusive thus far.…”

Section: Yesmentioning

confidence: 99%

Brown and beige fat: development, function and therapeutic potential

Harms

Seale

2013

Nat Med

1,992

2,054

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Adipose tissue, best known for its role in fat storage, can also suppress weight gain and metabolic disease through the action of specialized, heat-producing adipocytes. Brown adipocytes are located in dedicated depots and express constitutively high levels of thermogenic genes, whereas inducible 'brown-like' adipocytes, also known as beige cells, develop in white fat in response to various activators. The activities of brown and beige fat cells reduce metabolic disease, including obesity, in mice and correlate with leanness in humans. Many genes and pathways that regulate brown and beige adipocyte biology have now been identified, providing a variety of promising therapeutic targets for metabolic disease.npg

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Section: Yesmentioning

confidence: 99%

Brown and beige fat: development, function and therapeutic potential

Harms

Seale

2013

Nat Med

1,992

2,054

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“…Serendipitously, the diagnostic use of PET/CT scanning of human patients has identified depots of active beige fat [and more recently, also of brown adipose (7,15,20)] in sites in the neck and subclavicular area and along the spinal cord by enhanced uptake of the glucose analog [18F]deoxy-D-glucose at these sites (27). The uptake of brown/beige fat in humans is also dependent on cold exposure and adiposity, thus implying that similar processes may be operating in humans to regulate energy expenditure (34,35).…”

mentioning

confidence: 99%

Rorα deficiency and decreased adiposity are associated with induction of thermogenic gene expression in subcutaneous white adipose and brown adipose tissue

Lau

Tuong

Wang

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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deficiency and decreased adiposity are associated with induction of thermogenic gene expression in subcutaneous white adipose and brown adipose tissue. Am J Physiol Endocrinol Metab 308: E159-E171, 2015. First published November 25, 2014; doi:10.1152/ajpendo.00056.2014.-The Rarrelated orphan receptor-␣ (Ror␣) is a nuclear receptor that regulates adiposity and is a potential regulator of energy homeostasis. We have demonstrated that the Ror␣-deficient staggerer (sg/sg) mice display a lean and obesity-resistant phenotype. Adaptive Ucp1-dependent thermogenesis in beige/brite and brown adipose tissue serves as a mechanism to increase energy expenditure and resist obesity. DEXA and MRI analysis demonstrated significantly decreased total fat mass and fat/lean mass tissue ratio in male chow-fed sg/sg mice relative to wt mice. In addition, we observed increased Ucp1 expression in brown adipose and subcutaneous white adipose tissue but not in visceral adipose tissue from Ror␣-deficient mice. Moreover, this was associated with significant increases in the expression of the mRNAs encoding the thermogenic genes (i.e., markers of brown and beige adipose) Ppar␣, Err␣, Dio2, Acot11/Bfit, Cpt1␤, and Cidea in the subcutaneous adipose in the sg/sg relative to WT mice. These changes in thermogenic gene expression involved the significantly increased expression of the (cell-fate controlling) histone-lysine N-methyltransferase 1 (Ehmt1), which stabilizes the Prdm16 transcriptional complex. Moreover, primary brown adipocytes from sg/sg mice displayed a higher metabolic rate, and further analysis was consistent with increased uncoupling. Finally, core body temperature analysis and infrared thermography demonstrated that the sg/sg mice maintained greater thermal control and cold tolerance relative to the WT littermates. We suggest that enhanced Ucp1 and thermogenic gene expression/activity may be an important contributor to the lean, obesityresistant phenotype in Ror␣-deficient mice.retinoic acid receptor-related orphan receptor-␣; obesity; adiposity; adipose tissue; uncoupling protein-1 OBESITY IS A METABOLIC DISEASE that affects more than 10% of the global population. Energy imbalance as a result of excess dietary energy intake or genetic susceptibility results in increased energy storage and adiposity. Current strategies to ameliorate this disease include increasing energy expenditure through physical exercise and reducing energy consumption. However, the success rate is limited by compliance and the genetic disposition to maintain energy balance.Adaptive thermogenesis is an adrenergic/sympathetic-dependent mechanism utilized by mammals to increase energy expenditure in response to excessive dietary intake and/or cold stimulus. Thermogenesis occurs in both brown adipose tissue and beige fat [white adipose tissue cells that acquire a brown adipose phenotype (37, 41)]. This process involves increased (fatty acid-dependent) expression and activity of the thermogenic mitochondrial uncoupling protein (Ucp1). The function of Ucp1 is to me...

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“…Secondly, the samples obtained are usually very heterogeneous in the amount of BAT that they contain, analyzed as UCP1 expression levels. [14][15][16][17] If the samples used are very heterogeneous in their amount of BAT, this will increase the variability of any parameter analyzed. Hence, discrete differences in brown adipocytes compared to white adipocytes may be missed due to sample heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

“…Some examples of reference genes that has been used is TATAbinding protein (TBP), 14,18 cyclophilin A (PPIA), 13,19 b actin (ACTB), 15,20 glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 13 large ribosomal protein P0 (RPLP0) 16,17 and 18S rRNA. 21 In our study, all these reference genes, with the exception of 18S, seemed reasonable robust.…”

Section: Discussionmentioning

confidence: 99%