FGF21 is an Akt‐regulated myokine
Open accessAbstract
Fibroblast growth factor‐21 (FGF21) functions as a metabolic regulator. The FGF21 transcript is reported to be abundantly expressed in liver, but little is known about the regulation of FGF21 expression in other tissues. In this study, we show that levels of FGF21 protein expression were similar in skeletal muscle and liver from fasted mice. FGF21 transcript and protein expression were upregulated in gastrocnemius muscle of skeletal muscle‐specific Akt1 transgenic mice. Serum concentration of FGF21 was also increased by Akt1 transgene activation. In cultured skeletal muscle cells, FGF21 expression and secretion was regulated by insulin, Akt transduction and LY294002. These data indicate that skeletal muscle is a source of FGF21 and that its expression is regulated by a phosphatidylinosistol 3‐kinase (PI3‐kinase)/Akt1 signaling pathway‐dependent mechanism.
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FGF-21 is regulated by insulin through PI3K/Akt1 signaling pathway.
“Fibroblast growth factor-21 is regulated by insulin285 through the PI3K/Akt1 signaling pathway.286”
From Pancreatic regulation of glucose homeostasis. (2016) · cites this paper as [286]
In healthy skeletal muscle, FGF21 expression is almost undetectable.
“In skeletal muscle, FGF21 expression, in healthy conditions, is almost undetectable, and therefore, the circulating FGF21 is predominantly produced and released by the liver.6, 12”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [6]
Starvation is one of the stress conditions known to induce FGF21 expression in the liver, white adipose tissue, and skeletal muscle.
“Starvation is one of the stress conditions known to induce FGF21 expression in the liver,8, 32 WAT,10 and skeletal muscle (Figure 2A).6”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [6]
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 [6]
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 [6]
Circulating FGF21 is predominantly produced and released by the liver.
“In skeletal muscle, FGF21 expression, in healthy conditions, is almost undetectable, and therefore, the circulating FGF21 is predominantly produced and released by the liver.6, 12”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [6]
FGF21 is a stress-induced myokine released under conditions of starvation, ER stress, mitochondrial dysfunction, obesity, mitochondrial myopathies, and aging.
“(ii) FGF21 is a stress‐induced myokine, which is released under conditions of starvation, ER stress, mitochondrial dysfunction, obesity, mitochondrial myopathies, and aging.6, 13, 14, 15, 16, 17, 18”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [6]
In genetic mouse models of cellular or mitochondrial stress, FGF21 production is increased from skeletal muscle, BAT, and cardiac tissue.
“For example, FGF21 production from skeletal muscle (56, 61, 103, 128), BAT (59), and cardiac tissue (143) is increased in genetic mouse models of cellular or mitochondrial stress.”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [56]
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- Authors
- Izumiya, Y., Bina, H. A., Ouchi, N., Akasaki, Y., Kharitonenkov, A., & Walsh, K.
- Affiliations
- Boston University (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Walsh, Kenneth
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2008-10-21
- Volume
- 582
- Issue
- 27
- Pages
- 3805-3810
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- PMC
- PMC2604129
- OpenAlex
- W2047726905
- Cited by
- 415
- References
- 31
- Citations by year
- 2026: 7 · 2025: 23 · 2024: 25 · 2023: 25 · 2022: 21 · 2021: 18 · 2020: 20 · 2019: 35 · 2018: 31 · 2017: 26 · 2016: 21 · 2015: 36 · 2014: 33 · 2013: 23 · 2012: 24
- FWCI
- 6.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG015052, R37AG015052, AG15052)
- National Heart, Lung, and Blood Institute (HL81587, HL77774, R01HL086785, P01HL081587, HL 86785, R01HL077774)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- FGF21, myokines, AKT1, skeletal muscle, PI3K/Akt signaling, insulin, gastrocnemius, metabolic regulation, fasting
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Animals, Cell Line, Chromones, Fibroblast Growth Factors, Insulin, Liver, Mice, Transgenic, Morpholines, Signal Transduction, Up-Regulation, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, Mice
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