| First Author | Yin Y | Year | 2022 |
| Journal | J Exp Med | Volume | 219 |
| Issue | 5 | PubMed ID | 35412553 |
| Mgi Jnum | J:346110 | Mgi Id | MGI:7384227 |
| Doi | 10.1084/jem.20212491 | Citation | Yin Y, et al. (2022) FNIP1 regulates adipocyte browning and systemic glucose homeostasis in mice by shaping intracellular calcium dynamics. J Exp Med 219(5):e20212491 |
| abstractText | Metabolically beneficial beige adipocytes offer tremendous potential to combat metabolic diseases. The folliculin interacting protein 1 (FNIP1) is implicated in controlling cellular metabolism via AMPK and mTORC1. However, whether and how FNIP1 regulates adipocyte browning is unclear. Here, we demonstrate that FNIP1 plays a critical role in controlling adipocyte browning and systemic glucose homeostasis. Adipocyte-specific ablation of FNIP1 promotes a broad thermogenic remodeling of adipocytes, including increased UCP1 levels, high mitochondrial content, and augmented capacity for mitochondrial respiration. Mechanistically, FNIP1 binds to and promotes the activity of SERCA, a main Ca2+ pump responsible for cytosolic Ca2+ removal. Loss of FNIP1 resulted in enhanced intracellular Ca2+ signals and consequential activation of Ca2+-dependent thermogenic program in adipocytes. Furthermore, mice lacking adipocyte FNIP1 were protected against high-fat diet-induced insulin resistance and liver steatosis. Thus, these findings reveal a pivotal role of FNIP1 as a negative regulator of beige adipocyte thermogenesis and unravel an intriguing functional link between intracellular Ca2+ dynamics and adipocyte browning. |
