| First Author | Paulo E | Year | 2021 |
| Journal | Cell Rep | Volume | 36 |
| Issue | 12 | Pages | 109742 |
| PubMed ID | 34551310 | Mgi Jnum | J:321449 |
| Mgi Id | MGI:6876858 | Doi | 10.1016/j.celrep.2021.109742 |
| Citation | Paulo E, et al. (2021) Brown adipocyte ATF4 activation improves thermoregulation and systemic metabolism. Cell Rep 36(12):109742 |
| abstractText | Cold-induced thermogenesis in endotherms demands adaptive thermogenesis fueled by mitochondrial respiration and Ucp1-mediated uncoupling in multilocular brown adipocytes (BAs). However, dietary regulation of thermogenesis in BAs isn't fully understood. Here, we describe that the deficiency of Leucine-rich pentatricopeptide repeat containing-protein (Lrpprc) in BAs reduces mtDNA-encoded ETC gene expression, causes ETC proteome imbalance, and abolishes the mitochondria-fueled thermogenesis. BA-specific Lrpprc knockout mice are cold resistant in a 4 degrees C cold-tolerance test in the presence of food, which is accompanied by the activation of transcription factor 4 (ATF4) and proteome turnover in BAs. ATF4 activation genetically by BA-specific ATF4 overexpression or physiologically by a low-protein diet feeding can improve cold tolerance in wild-type and Ucp1 knockout mice. Furthermore, ATF4 activation in BAs improves systemic metabolism in obesogenic environment regardless of Ucp1's action. Therefore, our study reveals a diet-dependent but Ucp1-independent thermogenic mechanism in BAs that is relevant to systemic thermoregulation and energy homeostasis. |
