Journal article
FGF21 targets pathways which enhance insulin sensitivity in brown adipose, but not skeletal muscle in mice
Endocrinology (Philadelphia), Vol.167(5), bqag040
05/2026
DOI: 10.1210/endocr/bqag040
PMID: 41926710
Abstract
Acute pharmacological administration of the endocrine hormone fibroblast growth factor 21 (FGF21) enhances insulin sensitivity. This acute insulin-sensitizing effect of FGF21 is mediated through direct signaling to brown adipose tissues. Since skeletal muscle is an important site of insulin-stimulated glucose intake and shares a common progenitor cell with brown adipocytes, we examined whether the beneficial effects of FGF21 administration could be enhanced by making skeletal muscle a FGF21-responsive target tissue. This was accomplished by ectopically expressing the FGF21 co-receptor, β-klotho, in skeletal muscle. Here, we demonstrate that under normal conditions, FGF21 does not enhance insulin-stimulated glucose uptake in skeletal muscle. In addition, generation of FGF21 responsiveness and direct signaling to skeletal muscle also has no effect on FGF21-mediated increases in whole-body or skeletal muscle insulin sensitivity. Instead, FGF21 uniquely signals to brown adipocytes to enhance insulin-stimulated glucose uptake. Therefore, to identify how FGF21 signals to brown adipocytes to enhance insulin sensitivity, we performed comprehensive phospho-proteomics in brown adipocytes in response to FGF21 and/or insulin. Our results indicate that FGF21 administration increases the phosphorylation of several proteins involved in the trafficking of GLUT4 in primary brown adipocytes. These results provide new insights into how FGF21 enhances insulin sensitivity.
Details
- Title: Subtitle
- FGF21 targets pathways which enhance insulin sensitivity in brown adipose, but not skeletal muscle in mice
- Creators
- Matthew C Juber - University of IowaSheps King-McAlpin - University of IowaPaul Buscaglia - University of MichiganJulien A Sebag - University of MichiganMatthew J Potthoff - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.167(5), bqag040
- DOI
- 10.1210/endocr/bqag040
- PMID
- 41926710
- NLM abbreviation
- Endocrinology
- ISSN
- 1945-7170
- eISSN
- 1945-7170
- Publisher
- Oxford University Press
- Grant note
- National Institutes of Health (NIH): R01DK106104, R01AG083950 Veterans Affairs Merit Review Program: I01BX004634
This work was funded by the National Institutes of Health (NIH) R01DK106104 (M.J.P.), R01AG083950 (M.J.P.), and the Veterans Affairs Merit Review Program I01BX004634 (M.J.P.). We kindly thank the Thermo Fisher Scientific Center for Multiplexed Proteomics at Harvard Medical School for collecting the mass spectrometry data. We also thank Dr. Sharon Jensen-Cody, PhD, for assistance with tissue images.
- Language
- English
- Electronic publication date
- 04/02/2026
- Date published
- 05/2026
- Academic Unit
- Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9985149085302771
Metrics
1 Record Views