美国索尔克生物研究所Ronald M. Evans、Michael Downes等研究人员合作发现，成纤维细胞生长因子1（FGF1）和胰岛素共同控制脂肪分解。相关论文发表在2022年1月4日出版的《细胞—代谢》杂志上。

Title: FGF1 and insulin control lipolysis by convergent pathways

Author: Gencer Sancar, Sihao Liu, Emanuel Gasser, Jacqueline G. Alvarez, Christopher Moutos, Kyeongkyu Kim, Tim van Zutphen, Yuhao Wang, Timothy F. Huddy, Brittany Ross, Yang Dai, David Zepeda, Brett Collins, Emma Tilley, Matthew J. Kolar, Ruth T. Yu, Annette R. Atkins, Theo H. van Dijk, Alan Saghatelian, Johan W. Jonker, Michael Downes, Ronald M. Evans

Issue&Volume: 2022/01/04

Abstract: Inexorable increases in insulin resistance, lipolysis, and hepatic glucose production(HGP) are hallmarks of type 2 diabetes. Previously, we showed that peripheral deliveryof exogenous fibroblast growth factor 1 (FGF1) has robust anti-diabetic effects mediatedby the adipose FGF receptor (FGFR) 1. However, its mechanism of action is not known.Here, we report that FGF1 acutely lowers HGP by suppressing adipose lipolysis. Ona molecular level, FGF1 inhibits the cAMP-protein kinase A axis by activating phosphodiesterase4D (PDE4D), which separates it mechanistically from the inhibitory actions of insulinvia PDE3B. We identify Ser44 as an FGF1-induced regulatory phosphorylation site inPDE4D that is modulated by the feed-fast cycle. These findings establish the FGF1/PDE4pathway as an alternate regulator of the adipose-HGP axis and identify FGF1 as anunrecognized regulator of fatty acid homeostasis.

DOI: 10.1016/j.cmet.2021.12.004

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00623-9