Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle
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Fatty acids are the primary fuel source for skeletal muscle during most of our daily activities, and impaired fatty acid oxidation (FAO) is associated with insulin resistance. We have developed a mouse model of impaired FAO by deleting carnitine palmitoyltransferase-1b specifically in skeletal muscle (Cpt1b(m-/-)). Cpt1b(m-/-) mice have increased glucose utilization and are resistant to diet-induced obesity. Here, we show that inhibition of mitochondrial FAO induces FGF21 expression specifically in skeletal muscle. The induction of FGF21 in Cpt1b-deficient muscle is dependent on AMPK and Akt1 signaling but independent of the stress signaling pathways. FGF21 appears to act in a paracrine manner to increase glucose uptake under low insulin conditions, but it does not contribute to the resistance to diet-induced obesity.
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Muscle-dependent systemic release of FGF21 increases with starvation, endoplasmic reticulum stress, mitochondrial dysfunction, obesity, mitochondrial myopathies, and aging.
“In contrast, muscle‐dependent systemic release of FGF21 increases with starvation, endoplasmic reticulum stress, mitochondrial dysfunction, obesity, mitochondrial myopathies, and aging.6, 13, 14, 15, 16, 17, 18, 19”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [19]
Skeletal muscle is not only a producer but also a target of FGF21 because it expresses the cofactor β-klotho and the FGFRs.
“Recent studies reported that skeletal muscle is not only a producer but also a target of FGF21 because it expresses the cofactor β‐klotho and the FGFRs.6, 13, 14, 17, 18, 19”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [19]
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Self-citationFGF21 regulates insulin sensitivity following long-term chronic stress
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Self-citationHormonal factors in the control of the browning of white adipose tissue
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Advances in Biological Functions and Clinical Studies of FGF21
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Fibroblast Growth Factor 21: A Fascinating Perspective on the Regulation of Muscle Metabolism
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Use of antisense oligonucleotides to correct the splicing error in ISCU myopathy patient cell lines
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Self-citationTissue specific roles of fatty acid oxidation
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- Authors
- Vandanmagsar, B., Warfel, J. D., Wicks, S. E., Ghosh, S., Salbaum, J. M., Burk, D., Dubuisson, O. S., Mendoza, T. M., Zhang, J., Noland, R. C., & Mynatt, R. L.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Mynatt, Randall L.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 15
- Issue
- 8
- Pages
- 1686-1699
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4880522
- OpenAlex
- W2350983772
- Cited by
- 92
- References
- 58
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 11 · 2023: 12 · 2022: 6 · 2021: 10 · 2020: 12 · 2019: 9 · 2018: 10 · 2017: 9 · 2016: 4
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Civil War Book Review (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Louisiana Clinical and Translational Science Center
- National Institutes of Health
- National Institute of General Medical Sciences (P20GM103528, P30GM118430, U54GM104940)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK089641, R01DK098687, R01DK103860, T32DK064584, P30DK072476)
- National Center for Research Resources (P20RR021945)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mitochondrial fatty acid oxidation, FGF21, skeletal muscle, carnitine palmitoyltransferase 1b, AMPK signaling, AKT1 signaling, insulin resistance, glucose uptake, paracrine signaling, diet-induced obesity
- MeSH terms
- Adenylate Kinase, Animals, Adipose Tissue, Brown, Carnitine O-Palmitoyltransferase, Energy Metabolism, Fibroblast Growth Factors, Glucose, Humans, Insulin, Insulin-Like Growth Factor I, Mitochondria, Organ Size, Oxidation-Reduction, Stress, Physiological, Signal Transduction, Muscle, Skeletal, Adiposity, Lipid Metabolism, Proto-Oncogene Proteins c-akt, Mice, Adiponectin, Adipose Tissue, White, TOR Serine-Threonine Kinases
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