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AMPK/α-Ketoglutarate Axis Dynamically Mediates DNA Demethylation in the Prdm16 Promoter and Brown Adipogenesis.
Yang, Qiyuan; Liang, Xingwei; Sun, Xiaofei; Zhang, Lupei; Fu, Xing; Rogers, Carl J; Berim, Anna; Zhang, Shuming; Wang, Songbo; Wang, Bo; Foretz, Marc; Viollet, Benoit; Gang, David R; Rodgers, Buel D; Zhu, Mei-Jun; Du, Min.
Affiliation
  • Yang Q; Washington Center for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.
  • Liang X; Washington Center for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.
  • Sun X; School of Food Sciences, Washington State University, Pullman, WA 99164, USA.
  • Zhang L; Washington Center for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA; Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China.
  • Fu X; Washington Center for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.
  • Rogers CJ; Washington Center for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.
  • Berim A; Institute of Biological Chemistry, Washington State University, Pullman, WA 99164, USA.
  • Zhang S; School of Food Sciences, Washington State University, Pullman, WA 99164, USA.
  • Wang S; Washington Center for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.
  • Wang B; Washington Center for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.
  • Foretz M; INSERM U1016, Institut Cochin, 75014 Paris, France; CNRS UMR 8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
  • Viollet B; INSERM U1016, Institut Cochin, 75014 Paris, France; CNRS UMR 8104, 75014 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, 75006 Paris, France.
  • Gang DR; Institute of Biological Chemistry, Washington State University, Pullman, WA 99164, USA.
  • Rodgers BD; Washington Center for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.
  • Zhu MJ; School of Food Sciences, Washington State University, Pullman, WA 99164, USA.
  • Du M; Washington Center for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA; Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing 100194, C
Cell Metab ; 24(4): 542-554, 2016 10 11.
Article in En | MEDLINE | ID: mdl-27641099
Promoting brown adipose tissue (BAT) development is an attractive strategy for the treatment of obesity, as activated BAT dissipates energy through thermogenesis; however, the mechanisms controlling BAT formation are not fully understood. We hypothesized that as a master regulator of energy metabolism, AMP-activated protein kinase (AMPK) may play a direct role in the process and found that AMPKα1 (PRKAA1) ablation reduced Prdm16 expression and impaired BAT development. During early brown adipogenesis, the cellular levels of α-ketoglutarate (αKG), a key metabolite required for TET-mediated DNA demethylation, were profoundly increased and required for active DNA demethylation of the Prdm16 promoter. AMPKα1 ablation reduced isocitrate dehydrogenase 2 activity and cellular αKG levels. Remarkably, postnatal AMPK activation with AICAR or metformin rescued obesity-induced suppression of brown adipogenesis and thermogenesis. In summary, AMPK is essential for the epigenetic control of BAT development through αKG, thus linking a metabolite to progenitor cell differentiation and thermogenesis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription Factors / Adipose Tissue, Brown / Promoter Regions, Genetic / DNA Methylation / DNA-Binding Proteins / Adipogenesis / AMP-Activated Protein Kinases / Ketoglutaric Acids Limits: Animals Language: En Journal: Cell Metab Journal subject: METABOLISMO Year: 2016 Document type: Article Affiliation country: United States Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Transcription Factors / Adipose Tissue, Brown / Promoter Regions, Genetic / DNA Methylation / DNA-Binding Proteins / Adipogenesis / AMP-Activated Protein Kinases / Ketoglutaric Acids Limits: Animals Language: En Journal: Cell Metab Journal subject: METABOLISMO Year: 2016 Document type: Article Affiliation country: United States Country of publication: United States