Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

Publication date: Available online 3 March 2016
Source:Cell Reports
Author(s): Santiago Vernia, Julie Cavanagh-Kyros, Tamera Barrett, Cathy Tournier, Roger J. Davis
The cJun NH2-terminal kinase (JNK)-signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21) is a target of the hepatic JNK-signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21 deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. Moreover, the protective effects of hepatic JNK deficiency to suppress metabolic syndrome in high-fat diet-fed mice were not observed in mice with hepatocyte-specific FGF21 deficiency, including reduced blood glucose concentration and reduced intolerance to glucose and insulin. Furthermore, we show that JNK contributes to the regulation of hepatic FGF21 expression during fasting/feeding cycles. These data demonstrate that the hepatokine FGF21 is a key mediator of JNK-regulated metabolic syndrome.

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Teaser

Vernia et al. examine the role of circulating FGF21 in the response to JNK signaling. Hepatic JNK deficiency promotes expression of FGF21 and improves glycemia. Liver-specific ablation of the Fgf21 gene prevents this improvement of glycemia. These data argue that FGF21 mediates metabolic actions of hepatic JNK.


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