Cellular mechanisms by which FGF21 improves insulin sensitivity in male mice.

Details

Serval ID
serval:BIB_3D927EE23D2B
Type
Article: article from journal or magazin.
Collection
Publications
Title
Cellular mechanisms by which FGF21 improves insulin sensitivity in male mice.
Journal
Endocrinology
Author(s)
Camporez J.P., Jornayvaz F.R., Petersen M.C., Pesta D., Guigni B.A., Serr J., Zhang D., Kahn M., Samuel V.T., Jurczak M.J., Shulman G.I.
ISSN
1945-7170 (Electronic)
ISSN-L
0013-7227
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
154
Number
9
Pages
3099-3109
Language
english
Abstract
Fibroblast growth factor 21 (FGF21) is a potent regulator of glucose and lipid metabolism and is currently being pursued as a therapeutic agent for insulin resistance and type 2 diabetes. However, the cellular mechanisms by which FGF21 modifies insulin action in vivo are unclear. To address this question, we assessed insulin action in regular chow- and high-fat diet (HFD)-fed wild-type mice chronically infused with FGF21 or vehicle. Here, we show that FGF21 administration results in improvements in both hepatic and peripheral insulin sensitivity in both regular chow- and HFD-fed mice. This improvement in insulin responsiveness in FGF21-treated HFD-fed mice was associated with decreased hepatocellular and myocellular diacylglycerol content and reduced protein kinase Cε activation in liver and protein kinase Cθ in skeletal muscle. In contrast, there were no effects of FGF21 on liver or muscle ceramide content. These effects may be attributed, in part, to increased energy expenditure in the liver and white adipose tissue. Taken together, these data provide a mechanism by which FGF21 protects mice from lipid-induced liver and muscle insulin resistance and support its development as a novel therapy for the treatment of nonalcoholic fatty liver disease, insulin resistance, and type 2 diabetes.
Keywords
Adipose Tissue, Brown/drug effects, Adipose Tissue, Brown/metabolism, Animals, Cells, Cultured, Diet, High-Fat/adverse effects, Drug Implants, Energy Metabolism/drug effects, Fibroblast Growth Factors/administration & dosage, Fibroblast Growth Factors/metabolism, Glucose Intolerance/drug therapy, Glucose Intolerance/etiology, Humans, Infusions, Subcutaneous, Insulin Resistance, Isoenzymes/metabolism, Lipectomy, Lipid Metabolism/drug effects, Liver/drug effects, Liver/metabolism, Male, Mice, Mice, Inbred C57BL, Muscle, Skeletal/drug effects, Muscle, Skeletal/metabolism, Protein Kinase C/metabolism, Protein Kinase C-epsilon/metabolism, Recombinant Proteins/administration & dosage, Recombinant Proteins/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
10/09/2015 12:05
Last modification date
20/08/2019 13:33
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