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. 2025 May 6;37(5):1206-1222.e8.
doi: 10.1016/j.cmet.2025.03.002. Epub 2025 Mar 31.

Ceramide-induced FGF13 impairs systemic metabolic health

Jamal Naderi  1 , Amanda Kelsey Johnson  1 , Himani Thakkar  1 , Bhawna Chandravanshi  1 , Alec Ksiazek  1 , Ajay Anand  1 , Vinnyfred Vincent  1 , Aaron Tran  1 , Anish Kalimireddy  1 , Pratibha Singh  1 , Ayushi Sood  1 , Aasthika Das  1 , Chad Lamar Talbot  2 , Isabella A Distefano  3 , J Alan Maschek  2 , James Cox  4 , Ying Li  2 , Scott A Summers  5 , Donald J Atkinson  2 , Tursun Turapov  2 , Jason A Ratcliff  6 , Javis Fung  7 , Asim Shabbir  7 , M Shabeer Yassin  8 , Sue-Anne Toh Ee Shiow  8 , William L Holland  5 , Geoffrey S Pitt  3 , Bhagirath Chaurasia  9
Affiliations

Ceramide-induced FGF13 impairs systemic metabolic health

Jamal Naderi et al. Cell Metab. .

Abstract

Ceramide accumulation impairs adipocytes' ability to efficiently store and utilize nutrients, leading to energy and glucose homeostasis deterioration. Using a comparative transcriptomic screen, we identified the non-canonical, non-secreted fibroblast growth factor FGF13 as a ceramide-regulated factor that impairs adipocyte function. Obesity robustly induces FGF13 expression in adipose tissue in mice and humans and is positively associated with glycemic indices of type 2 diabetes. Pharmacological or genetic inhibition of ceramide biosynthesis reduces FGF13 expression. Using mice with loss and gain of function of FGF13, we demonstrate that FGF13 is both necessary and sufficient to impair energy and glucose homeostasis independent of ceramides. Mechanistically, FGF13 exerts these effects by inhibiting mitochondrial content and function, metabolic elasticity, and caveolae formation, which cumulatively impairs glucose utilization and thermogenesis. These studies suggest the therapeutic potential of targeting FGF13 to prevent and treat metabolic diseases.

Keywords: FGF13; adipocytes; ceramides; diabetes; insulin resistance; lipotoxicity; obesity; sphingolipids.

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Conflict of interest statement

Declaration of interests S.A.S. is a consultant and shareholder with Centaurus Therapeutics.

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