Journal article
Ceramide-induced FGF13 impairs systemic metabolic health
Cell metabolism, Vol.37(5), pp.1206-1222.e8
05/2025
DOI: 10.1016/j.cmet.2025.03.002
PMCID: PMC12058412
PMID: 40169001
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.
Details
- Title: Subtitle
- Ceramide-induced FGF13 impairs systemic metabolic health
- Creators
- Jamal Naderi - University of IowaAmanda Kelsey Johnson - Division of Endocrinology, Department of Internal Medicine, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USAHimani Thakkar - University of IowaBhawna Chandravanshi - Division of Endocrinology, Department of Internal Medicine, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USAAlec Ksiazek - Division of Endocrinology, Department of Internal Medicine, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USAAjay Anand - University of IowaVinnyfred Vincent - University of IowaAaron Tran - University of IowaAnish Kalimireddy - University of IowaPratibha Singh - University of IowaAyushi Sood - University of IowaAasthika Das - Division of Endocrinology, Department of Internal Medicine, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USAChad Lamar Talbot - University of UtahIsabella A Distefano - Weill Cornell MedicineJ Alan Maschek - University of UtahJames Cox - University of UtahYing Li - University of UtahScott A Summers - University of UtahDonald J Atkinson - University of UtahTursun Turapov - University of UtahJason A Ratcliff - University of IowaJavis Fung - National University Health SystemAsim Shabbir - National University Health SystemM Shabeer Yassin - National University Health SystemSue-Anne Toh Ee Shiow - National University of SingaporeWilliam L Holland - University of UtahGeoffrey S Pitt - Weill Cornell MedicineBhagirath Chaurasia - Division of Endocrinology, Department of Internal Medicine, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA 52242, USA. Electronic address: bhagirath-chaurasia@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Cell metabolism, Vol.37(5), pp.1206-1222.e8
- DOI
- 10.1016/j.cmet.2025.03.002
- PMID
- 40169001
- PMCID
- PMC12058412
- NLM abbreviation
- Cell Metab
- ISSN
- 1932-7420
- eISSN
- 1932-7420
- Publisher
- CELL PRESS
- Grant note
- Metabolic Phenotyping Cores at the Health Sciences Centre of the University of UtahUniversity of IowaNational Institutes of Health: DK115824, DK116888, DK116450, HL160089, DK112826, DK130296, DK124326 American Diabetes Association: 7-22-ICTSPM-24, 7-21-JDF-033 Diabetes Action Research and Education Foundation: 522 USDA: 2019-67018-29250 Roy J. Carver Charitable Trust: 25-5906 Washington University DRC: P30 DK 020579
We are grateful for support from the Metabolomics, Histology, Imaging, Geno-mics, and Metabolic Phenotyping Cores at the Health Sciences Centre of the University of Utah and the University of Iowa. We acknowledge the University of Utah Transgenic and Gene Targeting Mouse Core for generating the TRE-FGF13 transgenic targeted mice used in this research. We thank Dr. Philipp Scherer at the University of Texas Southwestern Medical Centre for providing the Adipoq-rtTA mice. The authors received research support from the National Institutes of Health (DK115824, DK116888, and DK116450 to S.A.S.; HL160089 to G.S.P.; DK112826 and DK130296 to W.L.H.; and DK124326 to B. Chaurasia) , the American Diabetes Association (7-22-ICTSPM-24 to W.L.H. and 7-21-JDF-033 to B. Chaurasia) , the Diabetes Action Research and Education Foundation (522 to B. Chaurasia) , the USDA (2019-67018-29250 to B. Chaurasia) , the Roy J. Carver Charitable Trust (#25-5906 to B. Chaurasia) , and a pilot grant from Washington University DRC (P30 DK 020579 to B. Chaurasia) .
- Language
- English
- Electronic publication date
- 03/26/2025
- Date published
- 05/2025
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine; Iowa Institute of Human Genetics
- Record Identifier
- 9984803811802771
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