Human BAT Possesses Molecular Signatures That Resemble Beige/Brite Cells

By Louis Z. Sharp, Kosaku Shinoda, H. Ohno, David W. Scheel, E. Tomoda, L. Ruiz, H. Hu, Larry L. Wang, Z. Pavlova, V. Gilsanz and 1 more. PLoS ONE, 2012

660 citations recorded by the source corpus.

Brown adipose tissue (BAT) dissipates chemical energy and generates heat to protect animals from cold and obesity. Rodents possess two types of UCP-1 positive brown adipocytes arising from distinct developmental lineages: “classical” brown adipocytes develop during the prenatal stage whereas “beige” or “brite” cells that reside in white adipose tissue (WAT) develop during the postnatal stage in response to chronic cold or PPARγ agonists. Beige cells’ inducible characteristics make them a promising therapeutic target for obesity treatment, however, the relevance of this cell type in humans remains unknown. In the present study, we determined the gene signatures that were unique to classical brown adipocytes and to beige cells induced by a specific PPARγ agonist rosiglitazone in mice. Subsequently we applied the transcriptional data to humans and examined the molecular signatures of human BAT isolated from multiple adipose depots. To our surprise, nearly all the human BAT abundantly expressed beige cell-selective genes, but the expression of classical brown fat-selective genes were nearly undetectable. Interestingly, expression of known brown fat-selective genes such as PRDM16 was strongly correlated with that of the newly identified beige cell-selective genes, but not with that of classical brown fat-selective genes. Furthermore, histological analyses showed that a new beige cell marker, CITED1, was selectively expressed in the UCP1-positive beige cells as well as in human BAT. These data indicate that human BAT may be primary composed of beige/brite cells.

Subfields: Epidemiology, Physiology, Rehabilitation

View Paper: https://www.semanticscholar.org/paper/d55739f5f2911c452367b6e72f4f4c3e5b3baa54

How researchers see this paper

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In Epidemiology

1. B. Spiegelman
2. S. Kajimura
3. E. Rosen
4. L. Sidossis
5. P. Seale
6. Gerald I. Shulman
7. Jun Wu
8. Haiming Cao

In Physiology

1. B. Spiegelman
2. S. Kajimura
3. P. Seale
4. L. Sidossis
5. E. Rosen
6. Jun Wu
7. P. Cohen
8. Kong Y. Chen

In Rehabilitation

1. S. Kajimura
2. L. Sidossis
3. B. Spiegelman
4. P. Seale
5. Gerald I. Shulman

Citations in the corpus

• Adaptive thermogenesis in adipocytes: is beige the new brown? (2013, background): “Gene expression analyses of autopsy samples of multiple human fat depots suggest that the majority of UCP1+ fat cells in humans show beige fat characteristics instead of brown (Sharp et al. 2012).”
• Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. (2014, background): “While stimulated beige adipocytes manifest thermogenic capacity similar to that of classic brown adipocytes, they are characterized by a distinct gene signature (Cypess et al., 2013; Jespersen et al., 2013; Sharp et al., 2012; Wu et al., 2012).”
• Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. (2013, positive): “(24) recently confirmed that human BAT can be categorized as beige/brite and not “classical” BAT.”
• Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders (2016, background): “Although it remains controversial whether mouse beige adipocytes have an equivalent cell population in human SAT, it has been demonstrated that human adult BAT consists of both classical brown adipocytes and beige adipocytes (52, 53).”
• Activation of Human Brown Adipose Tissue by a β3-Adrenergic Receptor Agonist (2015, neutral): “…constitutive ‘‘brown’’ adipocytes in the cervical and supraclavicular depots and the recruitable ‘‘beige/brite’’ adipocytes in the supraclavicular, abdominal, and other sites (Wu et al., 2012; Sharp et al., 2012; Lidell et al., 2013; Cypess et al., 2013; Jespersen et al., 2013; Sacks et al., 2013).”
• Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. (2015, positive): “On the other hand, BAT in the supraclavicular regions of infants and in adult humans expresses high levels of beige adipocyte-enriched genes, including Tbx1 , Cd137 , Tmem26 , and Cited1 (26, 27, 45).”
• Recruited brown adipose tissue as an antiobesity agent in humans. (2013, positive): “BAT in the supraclavicular region of human subjects was reported to be mainly composed of beige cells (22, 23).”
• Brown and beige fat: Physiological roles beyond heat-generation (2015, background): “Given the recent reports that adult human BAT largely contains beige-like adipocytes (Lee et al., 2014c; Sharp et al., 2012; Shinoda et al., 2015; Wu et al., 2012), understanding the molecular circuits that promoteWAT beige-ingmay lead to new therapeutic opportunities in obese and/or elderly people ”
• Ablation of PRDM16 and Beige Adipose Causes Metabolic Dysfunction and a Subcutaneous to Visceral Fat Switch (2014, background): “In light of the presence of beige fat cells in normal adult humans (Lidell et al., 2013; Sharp et al., 2012; Wu et al., 2012), these cells are an attractive target for the treatment of obesity and type 2 diabetes.”
• What We Talk About When We Talk About Fat (2014, positive): “In adult humans, the answer may depend on the specific depot sampled, as cells with both brown and beige attributes have been identified, with the brown:beige ratio increasing as one moves deeper within the neck and back (Cypess et al., 2013; Jespersen et al., 2013; Lidell et al., 2013; Sharp et al.”