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  • Metabolic Messengers
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Metabolic Messengers: fibroblast growth factor 1

Nature Metabolism volume 4, pages 663–671 (2022)Cite this article

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Abstract

While fibroblast growth factor (FGF) 1 is expressed in multiple tissues, only adipose-derived and brain FGF1 have been implicated in the regulation of metabolism. Adipose FGF1 production is upregulated in response to dietary stress and is essential for adipose tissue plasticity in these conditions. Similarly, in the brain, FGF1 secretion into the ventricular space and the adjacent parenchyma is increased after a hypercaloric challenge induced by either feeding or glucose infusion. Potent anorexigenic properties have been ascribed to both peripheral and centrally injected FGF1. The ability of recombinant FGF1 and variants with reduced mitogenicity to lower glucose, suppress adipose lipolysis and promote insulin sensitization elevates their potential as candidates in the treatment of type 2 diabetes mellitus and associated comorbidities. Here, we provide an overview of the known metabolic functions of endogenous FGF1 and discuss its therapeutic potential, distinguishing between peripherally or centrally administered FGF1.

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Fig. 1: Timeline of major FGF1-related discoveries.
Fig. 2: Mechanistic insights into the metabolic actions of FGF1.
Fig. 3: Target tissues and metabolic activity of exogenous FGF1.

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Acknowledgements

We thank A. Atkins and R. Yu for their assistance with reviewing the manuscript and thank C. Brondos for administrative assistance. This work was supported by grants from the Howard Hughes Medical Institute (to R.M.E.), NIH (DK057978) and the Nomis Foundation (Science of Health). R.M.E. holds the March of Dimes Chair in Molecular and Developmental Biology at the Salk Institute. E.G. was supported by a Swiss National Science Foundation (SNF) fellowship (P400PM_180759). G.S. was supported by a Deutsche Forschungsgemeinschaft (DFG) postdoctoral fellowship (SA 2991/1-1).

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  1. Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA

    Emanuel Gasser, Gencer Sancar, Michael Downes & Ronald M. Evans

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E.G., G.S., M.D. and R.M.E. researched data for the article and wrote the manuscript. All authors contributed to discussion of the content and reviewed and/or edited the manuscript before submission.

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Correspondence to Ronald M. Evans.

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M.D. and R.M.E are co-inventors of mutated FGF1 proteins and their methods of use, and may be entitled to royalties. All other authors declare no competing interests.

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Gasser, E., Sancar, G., Downes, M. et al. Metabolic Messengers: fibroblast growth factor 1. Nat Metab 4, 663–671 (2022). https://doi.org/10.1038/s42255-022-00580-2

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