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Updated: Oct 7, 2025
09:41
Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
Published on: March 17, 2023
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FGF1 and insulin control lipolysis by convergent pathways
Gencer Sancar1, Sihao Liu1, Emanuel Gasser1
1Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Cell Metabolism
|January 5, 2022
Summary
Fibroblast growth factor 1 (FGF1) lowers blood glucose by reducing fat breakdown and liver glucose production. This occurs via a novel FGF1/phosphodiesterase 4D (PDE4D) pathway, distinct from insulin signaling.
Area of Science:
- Metabolic disease research
- Endocrinology
- Molecular biology
Background:
- Type 2 diabetes is characterized by increased insulin resistance, lipolysis, and hepatic glucose production (HGP).
- Exogenous fibroblast growth factor 1 (FGF1) demonstrates anti-diabetic effects via adipose FGF receptor (FGFR) 1, but its mechanism remains unclear.
Purpose of the Study:
- To elucidate the molecular mechanism by which FGF1 exerts its anti-diabetic effects.
- To identify FGF1's role in regulating hepatic glucose production and adipose tissue metabolism.
Main Methods:
- Investigated FGF1's acute effects on hepatic glucose production and adipose lipolysis.
- Utilized molecular assays to determine the signaling pathways involved, focusing on cAMP-protein kinase A and phosphodiesterase 4D (PDE4D).
- Identified specific phosphorylation sites on PDE4D regulated by FGF1.
Main Results:
- FGF1 acutely suppresses hepatic glucose production by inhibiting adipose lipolysis.
- FGF1 activates phosphodiesterase 4D (PDE4D), inhibiting the cAMP-protein kinase A pathway, a mechanism distinct from insulin's action via PDE3B.
- Serine 44 was identified as a key FGF1-regulated phosphorylation site on PDE4D, influenced by the feed-fast cycle.
Conclusions:
- The FGF1/PDE4 pathway represents an alternative regulatory axis for adipose tissue and hepatic glucose production.
- FGF1 is identified as a novel regulator of fatty acid homeostasis and a potential therapeutic target for type 2 diabetes.
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