Fgf1, also known as acidic FGF (aFGF), is a single-chain polypeptide involved in regulating diverse biological processes from development to disease pathogenesis [2]. It is highly expressed in adult brain and kidney tissues. Functionally, it can regulate lipolysis, glucose metabolism, and has protective effects on various organs. It inhibits the cAMP-protein kinase A axis by activating phosphodiesterase 4D (PDE4D) to suppress adipose lipolysis, thus regulating the adipose-hepatic glucose production (HGP) axis [1].

Fgf1 knockout mice exhibit an aggressive diabetic phenotype and aberrant adipose tissue expansion when exposed to a high-fat diet, indicating its role in glucose and adipose metabolism [2]. Recombinant FGF1 (rFGF1) enhances mitochondrial oxidative phosphorylation (OXPHOS) and inhibits cardiomyocyte hypertrophy, and its administration can inhibit cardiac hypertrophy and fibrosis in pathological cardiac hypertrophy models [3]. These suggest that Fgf1 plays a crucial role in maintaining normal physiological functions related to metabolism and organ protection.

In conclusion, Fgf1 is essential for regulating fatty acid homeostasis, glucose metabolism, and protecting against organ-specific pathologies such as diabetes-related cardiomyopathy and pathological cardiac remodelling. The use of Fgf1 knockout mouse models has significantly advanced our understanding of its functions in these disease-related biological processes, providing potential therapeutic targets for diseases like type 2 diabetes and cardiac disorders.

References:

1. Sancar, Gencer, Liu, Sihao, Gasser, Emanuel, Downes, Michael, Evans, Ronald M. . FGF1 and insulin control lipolysis by convergent pathways. In Cell metabolism, 34, 171-183.e6. doi:10.1016/j.cmet.2021.12.004. https://pubmed.ncbi.nlm.nih.gov/34986332/

2. Jamal, Sahar B, Hockman, Dorit. 2024. FGF1. In Differentiation; research in biological diversity, 139, 100802. doi:10.1016/j.diff.2024.100802. https://pubmed.ncbi.nlm.nih.gov/39074995/

3. Li, Guoqi, Shao, Yihui, Guo, Hong Chang, Lai, Yong Qiang, Li, Yulin. . MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling. In Cardiovascular research, 118, 2139-2151. doi:10.1093/cvr/cvab248. https://pubmed.ncbi.nlm.nih.gov/34358309/