New Key Publication: FGF1 and insulin control lipolysis by convergent pathways
Cell Metabolism: Summary
Inexorable increases in insulin resistance, lipolysis, and hepatic glucose production (HGP) are hallmarks of type 2 diabetes. Previously, we showed that peripheral delivery of exogenous fibroblast growth factor 1 (FGF1) has robust anti-diabetic effects mediated by 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. On a molecular level, FGF1 inhibits the cAMP-protein kinase A axis by activating phosphodiesterase 4D (PDE4D), which separates it mechanistically from the inhibitory actions of insulin via PDE3B. We identify Ser44 as an FGF1-induced regulatory phosphorylation site in PDE4D that is modulated by the feed-fast cycle. These findings establish the FGF1/PDE4 pathway as an alternate regulator of the adipose-HGP axis and identify FGF1 as an unrecognized regulator of fatty acid homeostasis
Authors:
- 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
ARTICLE| VOLUME 34, ISSUE 1, P171-183.E6, JANUARY 04, 2022 : https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00623-9
| Last modified: | 06 January 2022 09.47 a.m. |
More news
-
28 March 2023
A leap of faith: from research to enterprise
Having ideas, experimenting and trying things out, wanting to change society. For many researchers, all of this is day-to-day business. But what if you want to take your idea to market? This is a step that often does not come naturally to...
-
14 February 2023
Lift to the inclusive workplace
There is plenty of work, and yet people with a disability are still often sidelined. One plus one is two, or so you’d think: this is the perfect time to help this group of workers find a job. The intention is there, also within the University, but...
-
15 December 2022
Groningen contributes to major research initiative into energy-efficient information technology
The Dutch science funding agency NWO recently awarded a large research project into new concepts for energy-efficient information technology of no less than ten million euros