Journal article
FGF21 and GDF15 Act Synergistically to Regulate Systemic Metabolic Homeostasis in Mice Lacking OPA1 in Thermogenic Adipocytes
Obesity (Silver Spring, Md.), Vol.33(10), pp.1909-1920
10/2025
DOI: 10.1002/oby.70004
PMCID: PMC12477105
PMID: 40897647
Appears in UI Libraries Support Open Access
Abstract
Our previous studies showed that mice lacking the mitochondrial fusion protein optic atrophy 1 (OPA1 BKO) in brown adipose tissue (BAT) have high metabolic rates and are resistant to diet-induced obesity (DIO) via effects partially mediated by independent actions of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) secretion from BAT. We examined whether FGF21 and GDF15 act synergistically, contributing to the systemic metabolic adaptations reported in OPA1 BKO mice.
We generated mice simultaneously lacking the Opa1, Fgf21, and Gdf15 genes in thermogenic adipocytes (TKO) and assessed energy homeostasis and glucose metabolism after regular chow or high-fat diet feeding.
Young TKO mice fed regular chow had impaired glucose tolerance, while insulin sensitivity was unchanged. Notably, combined Fgf21 and Gdf15 deletion in OPA1 BKO significantly blunted the resistance to DIO and insulin resistance observed in OPA1 BKO mice.
FGF21 and GDF15 act synergistically to maintain glucose homeostasis and promote resistance to DIO in mice lacking OPA1 in BAT, highlighting the potential of combined therapies using FGF21 and GDF15 for the treatment of metabolic disorders.
Details
- Title: Subtitle
- FGF21 and GDF15 Act Synergistically to Regulate Systemic Metabolic Homeostasis in Mice Lacking OPA1 in Thermogenic Adipocytes
- Creators
- Joshua Peterson - University of IowaJayashree Jena - University of Iowa, Internal MedicineAyushi Sood - University of Iowa, Internal MedicineShelly Roitershtein - University of Iowa, Internal MedicineDavid Smith - University of Iowa, Internal MedicineRenata O Pereira - University of Iowa, Endocrinology and Metabolism
- Resource Type
- Journal article
- Publication Details
- Obesity (Silver Spring, Md.), Vol.33(10), pp.1909-1920
- DOI
- 10.1002/oby.70004
- PMID
- 40897647
- PMCID
- PMC12477105
- NLM abbreviation
- Obesity (Silver Spring)
- ISSN
- 1930-7381
- eISSN
- 1930-739X
- Publisher
- Wiley
- Grant note
- 15SDG25710438 / American Heart Association 25PRE1361334 / American Heart Association 25POST1377539 / American Heart Association NIH DK125405 / NIDDK NIH HHS T32DK112751-01 / NIDDK NIH HHS
- Language
- English
- Electronic publication date
- 09/02/2025
- Date published
- 10/2025
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984963937602771
Metrics
13 Record Views