| First Author | Fu H | Year | 2025 |
| Journal | Nat Commun | Volume | 17 |
| Issue | 1 | Pages | 809 |
| PubMed ID | 41402325 | Mgi Jnum | J:391470 |
| Mgi Id | MGI:8281112 | Doi | 10.1038/s41467-025-67515-9 |
| Citation | Fu H, et al. (2025) Multi-layered transcriptional control of glycogen metabolism coordinates thermogenic remodeling of white adipocytes in male mice. Nat Commun 17(1):809 |
| abstractText | Thermogenic activation of subcutaneous white adipocytes requires glycogen synthesis and turnover. Here we show that beta-adrenergic stimulation induces a distinct glycogen metabolism gene program in inguinal white adipose tissue in a cell-autonomous and adipocyte-specific manner. Among these, Gys2 and Ppp1r3c are rapidly induced following acute beta3-adrenergic receptor activation. We identify Gys2 as a direct transcriptional target of PKA-CREB signaling. In contrast, sustained expression of glycogen metabolism genes under chronic beta3-adrenergic activation requires the coactivator PGC1alpha, whose loss blunts glycogen accumulation and thermogenic capacity. Mechanistically, PGC1alpha cooperates with estrogen-related receptors (ERRs) to regulate chromatin accessibility and gene transcription. Although deletion of ERRalpha is compensated by ERRgamma, combined deletion of ERRalpha/beta/gamma abolishes expression of glycogen metabolism and thermogenic genes. Chromatin profiling confirm that ERRs directly control the glycogen metabolic program in beige adipocytes. Together, our results identify a multilayered transcriptional axis that sustains glycogen metabolism during beta-adrenergic activation in male mice. |
