Journal
JOURNAL OF ENDOCRINOLOGY
Volume 226, Issue 3, Pages 207-217Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-15-0136
Keywords
FGF21; insulin resistance; NAFLD; energy expenditure; obesity
Categories
Funding
- Swiss National Science Foundation/Swiss Foundation [PASMP3_132563]
- Helmut Horten Foundation
- Swiss National Science Foundation (SNF) [PASMP3_132563] Funding Source: Swiss National Science Foundation (SNF)
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Fibroblast growth factor 21 (FGF21) is an important regulator of hepatic glucose and lipid metabolism and represents a potential pharmacological agent for the treatment of type 2 diabetes and obesity. Mice fed a ketogenic diet (KD) develop hepatic insulin resistance in association with high levels of FGF21, suggesting a state of FGF21 resistance. To address the role of FGF21 in hepatic insulin resistance, we assessed insulin action in FGF21 whole-body knock-out (FGF21 KO) male mice and their littermate WT controls fed a KD. Here, we report that FGF21 KO mice have hepatic insulin resistance and increased hepatic glucose production associated with an increase in plasma glucagon levels. FGF21 KO mice are also hypometabolic and display increased fat mass compared with their WT littermates. Taken together, these findings support a major role of FGF21 in regulating energy expenditure and hepatic glucose and lipid metabolism, and its potential role as a candidate in the treatment of diseases associated with insulin resistance.
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