| First Author | Chen Y | Year | 2022 |
| Journal | Nat Metab | Volume | 4 |
| Issue | 9 | Pages | 1166-1184 |
| PubMed ID | 36123394 | Mgi Jnum | J:373688 |
| Mgi Id | MGI:8161363 | Doi | 10.1038/s42255-022-00631-8 |
| Citation | Chen Y, et al. (2022) Adipocyte IRE1alpha promotes PGC1alpha mRNA decay and restrains adaptive thermogenesis. Nat Metab 4(9):1166-1184 |
| abstractText | Adipose tissue undergoes thermogenic remodeling in response to thermal stress and metabolic cues, playing a crucial role in regulating energy expenditure and metabolic homeostasis. Endoplasmic reticulum (ER) stress is associated with adipose dysfunction in obesity and metabolic disease. It remains unclear, however, if ER stress-signaling in adipocytes mechanistically mediates dysregulation of thermogenic fat. Here we show that inositol-requiring enzyme 1alpha (IRE1alpha), a key ER stress sensor and signal transducer, acts in both white and beige adipocytes to impede beige fat activation. Ablation of adipocyte IRE1alpha promotes browning/beiging of subcutaneous white adipose tissue following cold exposure or beta3-adrenergic stimulation. Loss of IRE1alpha alleviates diet-induced obesity and augments the anti-obesity effect of pharmacologic beta3-adrenergic stimulation. Notably, IRE1alpha suppresses stimulated lipolysis and degrades Ppargc1a messenger RNA through its RNase activity to downregulate the thermogenic gene program. Hence, blocking IRE1alpha bears therapeutic potential in unlocking adipocytes' thermogenic capacity to combat obesity and metabolic disorders. |
