| First Author | Han JS | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 3268 |
| PubMed ID | 35672324 | Mgi Jnum | J:327519 |
| Mgi Id | MGI:7285474 | Doi | 10.1038/s41467-022-30925-0 |
| Citation | Han JS, et al. (2022) Adipocyte HIF2alpha functions as a thermostat via PKA Calpha regulation in beige adipocytes. Nat Commun 13(1):3268 |
| abstractText | Thermogenic adipocytes generate heat to maintain body temperature against hypothermia in response to cold. Although tight regulation of thermogenesis is required to prevent energy sources depletion, the molecular details that tune thermogenesis are not thoroughly understood. Here, we demonstrate that adipocyte hypoxia-inducible factor alpha (HIFalpha) plays a key role in calibrating thermogenic function upon cold and re-warming. In beige adipocytes, HIFalpha attenuates protein kinase A (PKA) activity, leading to suppression of thermogenic activity. Mechanistically, HIF2alpha suppresses PKA activity by inducing miR-3085-3p expression to downregulate PKA catalytic subunit alpha (PKA Calpha). Ablation of adipocyte HIF2alpha stimulates retention of beige adipocytes, accompanied by increased PKA Calpha during re-warming after cold stimuli. Moreover, administration of miR-3085-3p promotes beige-to-white transition via downregulation of PKA Calpha and mitochondrial abundance in adipocyte HIF2alpha deficient mice. Collectively, these findings suggest that HIF2alpha-dependent PKA regulation plays an important role as a thermostat through dynamic remodeling of beige adipocytes. |
