Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism

Qin, Hao; Yadav, Rachita; Basse, Astrid L.; Petersen, Sten; Sonne, Si Brask; Rasmussen, Simon; Zhu, Qianhua; Lu, Zhike; Wang, Jun; Audouze, Karine; Gupta, Ramneek; Madsen, Lise; Kristiansen, Karsten; Hansen, Jacob B.

doi:10.1152/ajpendo.00277.2014

Cited by 109 publications

(112 citation statements)

References 77 publications

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“…Overall, we show that cold exposure induced fat browning and activated mitochondrial function; these results are consistent with previous studies (23)(24)(25). Therefore, we also suggest that BLC shows comparable effects to cold stimulation on fat browning.…”

Section: Blc Enhances Mitochondrial Function and Mitochondrial Biogensupporting

confidence: 93%

“…4D). Previous studies have shown that activated mitochondrial function can be induced by cold stress or b-adrenergic stimuli as well as by the expression of brown adipocyte-specific genes (23)(24)(25). Exposure of mice to cold temperatures in this study resulted in an ;15-fold increase in UCP1 mRNA levels and a significant increase in UCP1 protein levels in the scWAT of mice compared with mice at room temperature ( Supplementary Fig.…”

Section: Blc Enhances Mitochondrial Function and Mitochondrial Biogenmentioning

confidence: 53%

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β-Lapachone Prevents Diet-Induced Obesity by Increasing Energy Expenditure and Stimulating the Browning of White Adipose Tissue via Downregulation of miR-382 Expression

et al. 2016

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There has been great interest in the browning of fat for the treatment of obesity. Although b-lapachone (BLC) has potential therapeutic effects on obesity, the fat-browning effect and thermogenic capacity of BLC on obesity have never been demonstrated. Here, we showed that BLC stimulated the browning of white adipose tissue (WAT), increased the expression of brown adipocyte-specific genes (e.g., uncoupling protein 1 [UCP1]), decreased body weight gain, and ameliorated metabolic parameters in mice fed a high-fat diet. Consistently, BLC-treated mice showed significantly higher energy expenditure compared with control mice. In vitro, BLC increased the expression of brown adipocyte-specific genes in stromal vascular fraction-differentiated adipocytes. BLC also controlled the expression of miR-382, which led to the upregulation of its direct target, Dio2. Upregulation of miR-382 markedly inhibited the differentiation of adipocytes into beige adipocytes, whereas BLC recovered beige adipocyte differentiation and increased the expression of Dio2 and UCP1. Our findings suggest that the BLC-mediated increase in the browning of WAT and the thermogenic capacity of BAT significantly results in increases in energy expenditure. Browning of WAT by BLC was partially controlled via the regulation of miR-382 targeting Dio2 and may lead to the prevention of diet-induced obesity.

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Section: Blc Enhances Mitochondrial Function and Mitochondrial Biogensupporting

confidence: 93%

Section: Blc Enhances Mitochondrial Function and Mitochondrial Biogenmentioning

confidence: 53%

β-Lapachone Prevents Diet-Induced Obesity by Increasing Energy Expenditure and Stimulating the Browning of White Adipose Tissue via Downregulation of miR-382 Expression

et al. 2016

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“…Allelic variants causing loss-of-function put human individuals at risk to develop obesity14. A comparison of our RNA-seq data with two microarray-based data sets78 and a digital gene expression profiling15 revealed that GPR120 was consistently and strongly upregulated in BAT following cold exposure. Here we set out to assess the regulation and function of GPR120 in relation to BAT activation.…”

Section: Resultsmentioning

confidence: 91%

The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes

et al. 2016

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The thermogenic activity of brown adipose tissue (BAT) and browning of white adipose tissue are important components of energy expenditure. Here we show that GPR120, a receptor for polyunsaturated fatty acids, promotes brown fat activation. Using RNA-seq to analyse mouse BAT transcriptome, we find that the gene encoding GPR120 is induced by thermogenic activation. We further show that GPR120 activation induces BAT activity and promotes the browning of white fat in mice, whereas GRP120-null mice show impaired cold-induced browning. Omega-3 polyunsaturated fatty acids induce brown and beige adipocyte differentiation and thermogenic activation, and these effects require GPR120. GPR120 activation induces the release of fibroblast growth factor-21 (FGF21) by brown and beige adipocytes, and increases blood FGF21 levels. The effects of GPR120 activation on BAT activation and browning are impaired in FGF21-null mice and cells. Thus, the lipid sensor GPR120 activates brown fat via a mechanism that involves induction of FGF21.

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“…It was recently shown that cold increases the expression of genes related to PPP in BAT72, a metabolic pathway required to sustain de novo lipogenesis and nucleotide biosynthesis. Here, we confirmed these findings in control mice.…”

Section: Discussionmentioning

confidence: 99%

mTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold

Labbé

Mouchiroud

Caron

et al. 2016

Sci Rep

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In response to cold, brown adipose tissue (BAT) increases its metabolic rate and expands its mass to produce heat required for survival, a process known as BAT recruitment. The mechanistic target of rapamycin complex 1 (mTORC1) controls metabolism, cell growth and proliferation, but its role in regulating BAT recruitment in response to chronic cold stimulation is unknown. Here, we show that cold activates mTORC1 in BAT, an effect that depends on the sympathetic nervous system. Adipocyte-specific mTORC1 loss in mice completely blocks cold-induced BAT expansion and severely impairs mitochondrial biogenesis. Accordingly, mTORC1 loss reduces oxygen consumption and causes a severe defect in BAT oxidative metabolism upon cold exposure. Using in vivo metabolic imaging, metabolomics and transcriptomics, we show that mTORC1 deletion impairs glucose and lipid oxidation, an effect linked to a defect in tricarboxylic acid (TCA) cycle activity. These analyses also reveal a severe defect in nucleotide synthesis in the absence of mTORC1. Overall, these findings demonstrate an essential role for mTORC1 in the regulation of BAT recruitment and metabolism in response to cold.

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Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism

Cited by 109 publications

References 77 publications

β-Lapachone Prevents Diet-Induced Obesity by Increasing Energy Expenditure and Stimulating the Browning of White Adipose Tissue via Downregulation of miR-382 Expression

β-Lapachone Prevents Diet-Induced Obesity by Increasing Energy Expenditure and Stimulating the Browning of White Adipose Tissue via Downregulation of miR-382 Expression

The lipid sensor GPR120 promotes brown fat activation and FGF21 release from adipocytes

mTORC1 is Required for Brown Adipose Tissue Recruitment and Metabolic Adaptation to Cold

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