Cited by 691Fibroblast Growth Factor ResearchAdipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and Metabolism

Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice

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Lin, Zhuofeng, Tian, Haishan, Lam, Karen S.L., Lin, Shaoqiang, Hoo, Ruby C.L., Konishi, Morichika, Itoh, Nobuyuki, Wang, Yu +3 more·2013·Cell Metabolism

Abstract

Fibroblast growth factor 21 (FGF21) is a metabolic hormone with pleiotropic effects on regulating glucose and lipid homeostasis and insulin sensitivity. However, the mechanisms underlying the metabolic actions of FGF21 remain unknown. Here we show that the insulin-sensitizing adipokine adiponectin is a downstream effector of FGF21. Treatments with FGF21 enhanced both expression and secretion of adiponectin in adipocytes, thereby increasing serum levels of adiponectin in mice. Adiponectin knockout mice were refractory to several therapeutic benefits of FGF21, including alleviation of obesity-associated hyperglycemia, hypertriglyceridemia, insulin resistance, and hepatic steatosis. Furthermore, the effects of FGF21 on attenuation of obesity-induced impairment in insulin signaling in liver and skeletal muscle were abrogated in adiponectin knockout mice, whereas FGF21-mediated activation of ERK1/ERK2 in adipose tissues remained unaffected. Therefore, adiponectin couples FGF21 actions in local adipocytes to liver and skeletal muscle, thereby mediating the systemic effects of FGF21 on energy metabolism and insulin sensitivity.

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Crossref · 10.1016/j.cmet.2013.04.005

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  • Hepatokines are a novel class of exercise-inducible soluble factors released by the liver during and after physical activity, including selenoprotein P, FGF21, HSP72, and hepassocin.

    “Hepatokines represent a novel class of exercise-inducible soluble factors released by the liver during and after physical activity, including selenoprotein P (SeP) [93], FGF21 [118], heat shock protein 72 (HSP72) [119], and hepassocin (HPS) (Figure 3) [120].”

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Authors
Lin, Z., Tian, H., Lam, K. S. L., Lin, S., Hoo, R. C. L., Konishi, M., Itoh, N., Wang, Y., Bornstein, S. R., Xu, A., & Li, X.
Affiliations
  • Wenzhou Medical University (CN)
  • University of Hong Kong (HK)
  • Kyoto University (JP)
Corresponding author
  • Xu, Aimin
  • Li, Xiaokun
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2013-05
Volume
17
Issue
5
Pages
779-789
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2100232436
Cited by
691
References
50
Citations by year
2026: 28 · 2025: 50 · 2024: 56 · 2023: 53 · 2022: 69 · 2021: 55 · 2020: 43 · 2019: 47 · 2018: 48 · 2017: 54 · 2016: 60 · 2015: 56 · 2014: 49 · 2013: 21
FWCI
27.79
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Site cant be reached (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
FGF21, adiponectin, insulin sensitivity, glucose homeostasis, insulin resistance, obesity, hypertriglyceridemia, hepatic steatosis, adipocytes, ERK1/ERK2 signaling, energy metabolism, metabolic hormones, adipokines, skeletal muscle insulin signaling
MeSH terms
Animals, Energy Metabolism, Fatty Acids, Fatty Liver, Fibroblast Growth Factors, Glucose, Homeostasis, Hyperglycemia, Insulin Resistance, Liver, Male, Mice, Inbred C57BL, Obesity, Oxidation-Reduction, Hypertriglyceridemia, Adipocytes, Muscle, Skeletal, MAP Kinase Signaling System, Mice, Adiponectin

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