Human brown adipose tissue: regulation and anti-obesity potential [Review]

Saito, Masayuki

doi:10.1507/endocrj.ej13-0527

Cited by 35 publications

(28 citation statements)

References 56 publications

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“…The second important implication of our work intersects with the widespread interest in modulating BAT function in the fight against obesity. It is currently thought that interventions that can increase BAT function, will lead to increased energy consumption by BAT, thereby decreasing body weight32. Using the reverse logic, if alcohol consumption impairs BAT function, could it therefore be contributing to decreased energy expenditure and the obesity epidemic?…”

Section: Discussionmentioning

confidence: 99%

Chronic alcohol consumption decreases brown adipose tissue mass and disrupts thermoregulation: a possible role for altered retinoid signaling

Blaner

Gao

Jiang

et al. 2017

Sci Rep

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Retinoic acid, an active metabolite of dietary vitamin A, acts as a ligand for nuclear receptor transcription factors with more than 500 known target genes. It is becoming increasingly clear that alcohol has a significant impact on cellular retinoic acid metabolism, with resultant effects on its function. Here, we test the hypothesis that chronic alcohol consumption impairs retinoic acid signaling in brown adipose tissue (BAT), leading to impaired BAT function and thermoregulation. All studies were conducted in age-matched, male mice consuming alcohol-containing liquid diets. Alcohol’s effect on BAT was assessed by histology, qPCR, HPLC, LC/MS and measures of core body temperature. Our data show that chronic alcohol consumption decreases BAT mass, with a resultant effect on thermoregulation. Follow-up mechanistic studies reveal a decreased triglyceride content in BAT, as well as impaired retinoic acid homeostasis, associated with decreased BAT levels of retinoic acid in alcohol-consuming mice. Our work highlights a hitherto uncharacterized effect of alcohol on BAT function, with possible implications for thermoregulation and energy metabolism in drinkers. Our data indicate that alcohol’s effects on brown adipose tissue may be mediated through altered retinoic acid signaling.

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Section: Discussionmentioning

confidence: 99%

Chronic alcohol consumption decreases brown adipose tissue mass and disrupts thermoregulation: a possible role for altered retinoid signaling

Blaner

Gao

Jiang

et al. 2017

Sci Rep

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“…Other than BMP7, some hormones and cytokines such as BDNF, FGF21, and FNDC5 (precursor of irisin) have been shown to increase brown adipogenesis and protect mice from obesity and diabetes [42]. Several studies have attempted to increase human beige adipogenesis by applying these secretory factors to human progenitor cells in vitro.…”

Section: Discussionmentioning

confidence: 99%

BMP7 Drives Human Adipogenic Stem Cells into Metabolically Active Beige Adipocytes

Okla

Temel

et al. 2014

Lipids

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Adult humans have a substantial amount of inducible-brown (or beige) fat, which is associated with increased energy expenditure and reduced weight gain via thermogenesis. Despite the identification of key regulators of beige adipogenesis, impacts of dietary factors on adaptive thermogenesis are largely unknown, partly due to a lack of validated human cell models. Bone morphogenetic protein 7 (BMP7) is known to promote brown adipogenesis in rodent and human progenitor cells. However, controversy still surrounds the cellular identity in BMP7-mediated transition of white to brown adipocytes. The aim of this study is to confirm BMP7-derived human adipocytes as a relevant in vitro model of human beige adipocyte by verifying the cellular lineage and metabolic activity. In this study, we hypothesized that pre-exposure of stromal vascular (SV) fraction of primary human adipogenic precursor cells (hASC) to BMP7 would convert metabolically active brown adipocytes. Our results showed that exposure of hASC to human BMP7 was associated with significant escalation of 1) UCP1 gene expression, a signature gene of brown adipocytes, 2) beige specific marker gene expression (i.e., CD137 and TMEM26), 3) glucose and fatty acid uptake, and 4) basal and cAMP-stimulated oxygen consumption rate compared to white adipocyte control. Taken together, we demonstrated that BMP7 mediates conversion of hASC into metabolically active beige adipocytes. By confirming the cellular identity and metabolic activity, this BMP7-induced human beige adipocytes from hASC should aid in the discovery and assessment of bioactive molecules to promote adaptive thermogenesis.

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“…High levels of brown/beige fat activity protect animals against many of the harmful effects of a high-fat diet, including obesity and insulin resistance (Harms and Seale 2013;Stanford et al 2013;Rosen and Spiegelman 2014). In people, brown/beige fat activity levels also correlate with reduced adiposity, and cold-stimulated brown/beige fat activity promotes weight loss (Saito 2014;Yoneshiro and Saito 2014). Thus, elucidating the molecular pathways that regulate brown/ beige fat activity may reveal new approaches to treat obesity and related diseases.…”

mentioning

confidence: 99%

PRDM16 binds MED1 and controls chromatin architecture to determine a brown fat transcriptional program

Harms¹,

et al. 2015

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PR (PRD1-BF1-RIZ1 homologous) domain-containing 16 (PRDM16) drives a brown fat differentiation program, but the mechanisms by which PRDM16 activates brown fat-selective genes have been unclear. Through chromatin immunoprecipitation (ChIP) followed by deep sequencing (ChIP-seq) analyses in brown adipose tissue (BAT), we reveal that PRDM16 binding is highly enriched at a broad set of brown fat-selective genes. Importantly, we found that PRDM16 physically binds to MED1, a component of the Mediator complex, and recruits it to superenhancers at brown fat-selective genes. PRDM16 deficiency in BAT reduces MED1 binding at PRDM16 target sites and causes a fundamental change in chromatin architecture at key brown fat-selective genes. Together, these data indicate that PRDM16 controls chromatin architecture and superenhancer activity in BAT.

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Human brown adipose tissue: regulation and anti-obesity potential [Review]

Cited by 35 publications

References 56 publications

Chronic alcohol consumption decreases brown adipose tissue mass and disrupts thermoregulation: a possible role for altered retinoid signaling

Chronic alcohol consumption decreases brown adipose tissue mass and disrupts thermoregulation: a possible role for altered retinoid signaling

BMP7 Drives Human Adipogenic Stem Cells into Metabolically Active Beige Adipocytes

PRDM16 binds MED1 and controls chromatin architecture to determine a brown fat transcriptional program

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