| First Author | Yang Q | Year | 2016 |
| Journal | Cell Metab | Volume | 24 |
| Issue | 4 | Pages | 542-554 |
| PubMed ID | 27641099 | Mgi Jnum | J:251930 |
| Mgi Id | MGI:6107146 | Doi | 10.1016/j.cmet.2016.08.010 |
| Citation | Yang Q, et al. (2016) AMPK/alpha-Ketoglutarate Axis Dynamically Mediates DNA Demethylation in the Prdm16 Promoter and Brown Adipogenesis. Cell Metab 24(4):542-554 |
| abstractText | 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 AMPKalpha1 (PRKAA1) ablation reduced Prdm16 expression and impaired BAT development. During early brown adipogenesis, the cellular levels of alpha-ketoglutarate (alphaKG), a key metabolite required for TET-mediated DNA demethylation, were profoundly increased and required for active DNA demethylation of the Prdm16 promoter. AMPKalpha1 ablation reduced isocitrate dehydrogenase 2 activity and cellular alphaKG 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 alphaKG, thus linking a metabolite to progenitor cell differentiation and thermogenesis. |
