Fibroblast growth factor-21 protects human skeletal muscle myotubes from palmitate-induced insulin resistance by inhibiting stress kinase and NF-κB

Fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism. We aimed to investigate the effect of an FGF21 analogue (LY2405319) on the development of atherosclerosis and its associated parameters. ApoE−/− mice were fed an atherogenic diet for 14 weeks and were randomly assigned to control (saline) or FGF21 (0.1 mg/kg) treatment group (n = 10/group) for 5 weeks. Plaque size in the aortic arch/valve areas and cardiovascular risk markers were evaluated in blood and tissues. The effects of FGF21 on various atherogenesis-related pathways were also assessed. Atherosclerotic plaque areas in the aortic arch/valve were significantly smaller in the FGF21 group than in controls after treatment. FGF21 significantly decreased body weight and glucose concentrations, and increased circulating adiponectin levels. FGF21 treatment alleviated insulin resistance and decreased circulating concentrations of triglycerides, which were significantly correlated with plaque size. FGF21 treatment reduced lipid droplets in the liver and decreased fat cell size and inflammatory cell infiltration in the abdominal visceral fat compared with the control group. The monocyte chemoattractant protein-1 levels were decreased and β-hydroxybutyrate levels were increased by FGF21 treatment. Uncoupling protein 1 expression in subcutaneous fat was greater and fat cell size in brown fat was smaller in the FGF21 group compared with controls. Administration of FGF21 showed anti-atherosclerotic effects in atherosclerosis-prone mice and exerted beneficial effects on critical atherosclerosis pathways. Improvements in inflammation and insulin resistance seem to be mechanisms involved in the mitigation of atherosclerosis by FGF21 therapy.

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Expression of Fibroblast Growth Factor-21 in Muscle Is Associated with Lipodystrophy, Insulin Resistance and Lipid Disturbances in Patients with HIV

PLoS ONE ◽

10.1371/journal.pone.0055632 ◽

2013 ◽

Vol 8 (3) ◽

pp. e55632 ◽

Cited By ~ 20

Author(s):

Birgitte Lindegaard ◽

Thine Hvid ◽

Thomas Grøndahl ◽

Christian Frosig ◽

Jan Gerstoft ◽

...

Keyword(s):

Insulin Resistance ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth

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Serum fibroblast growth factor 21 levels in gestational diabetes mellitus in relation to insulin resistance and dyslipidemia

Metabolism ◽

10.1016/j.metabol.2009.07.003 ◽

2010 ◽

Vol 59 (1) ◽

pp. 33-37 ◽

Cited By ~ 44

Author(s):

Sebastian Stein ◽

Holger Stepan ◽

Jürgen Kratzsch ◽

Michael Verlohren ◽

Hans-Joachim Verlohren ◽

...

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Growth Factor ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Fibroblast Growth Factor ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth

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Loss of fibroblast growth factor 21 action induces insulin resistance, pancreatic islet hyperplasia and dysfunction in mice

Cell Death and Disease ◽

10.1038/cddis.2015.80 ◽

2015 ◽

Vol 6 (3) ◽

pp. e1707-e1707 ◽

Cited By ~ 37

Author(s):

W Y So ◽

Q Cheng ◽

A Xu ◽

K S L Lam ◽

P S Leung

Keyword(s):

Insulin Resistance ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Pancreatic Islet ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Islet Hyperplasia

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Increased Circulating and Epicardial Adipose Tissue mRNA Expression of Fibroblast Growth Factor-21 After Cardiac Surgery: Possible Role in Postoperative Inflammatory Response and Insulin Resistance

Physiological Research ◽

10.33549/physiolres.932134 ◽

2011 ◽

pp. 757-767 ◽

Cited By ~ 20

Author(s):

T. KOTULÁK ◽

J. DRÁPALOVÁ ◽

P. KOPECKÝ ◽

Z. LACINOVÁ ◽

P. KRAMÁŘ ◽

...

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Cardiac Surgery ◽

Growth Factor ◽

Mrna Expression ◽

Fibroblast Growth Factor ◽

Serum Glucose ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Baseline Serum

We studied the changes in serum fibroblast growth factor-21 (FGF-21) concentrations, its mRNA, and protein expression in skeletal muscle and adipose tissue of 15 patients undergoing cardiac surgery. Blood samples were obtained: prior to initiation of anesthesia, prior to the start of extracorporeal circulation, upon completion of the surgery, and 6, 24, 48, and 96 hours after the end of the surgery. Tissue sampling was performed at the start and end of surgery. The mean baseline serum FGF-21 concentration was 63.1 (43.03-113.95) pg/ml and it increased during surgery with peak 6 hours after its end [385.5 (274.55-761.65) pg/ml, p<0.001], and returned to baseline value [41.4 (29.15-142.83) pg/ml] 96 hours after the end of the surgery. Serum glucose, insulin, CRP, IL-6, IL-8, MCP-1, and TNF-alpha concentrations significantly increased during the surgery. Baseline FGF-21 mRNA expression in skeletal muscle was higher than in both adipose tissue depots and it was not affected by the surgery. Epicardial fat FGF-21 mRNA increased after surgery. Muscle FGF-21 mRNA positively correlated with blood glucose levels at the end of the surgery. Our data suggest a possible role of FGF-21 in the regulation of glucose metabolism and insulin sensitivity in surgery-related stress.

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