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Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

Santiago Vernia1, Julie Cavanagh-Kyros2, Tamera Barrett2

  • 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Cell Reports
|March 8, 2016
PubMed

Insights

Fibroblast growth factor 21 (FGF21), regulated by cJun NH2-terminal kinase (JNK) signaling, mediates metabolic syndrome. FGF21 deficiency in the liver blocks JNK

Area of Science:

  • Metabolic signaling pathways
  • Hormonal regulation of metabolism
  • Molecular mechanisms of metabolic syndrome

Background:

  • The cJun NH2-terminal kinase (JNK) pathway is linked to metabolic syndrome, affecting blood glucose and insulin resistance.
  • Fibroblast growth factor 21 (FGF21) is a JNK target in the liver and may influence glucose regulation.

Purpose of the Study:

  • To investigate the role of hepatocyte-specific FGF21 in mediating the effects of JNK signaling on metabolic syndrome.
  • To determine if FGF21 is essential for the protective metabolic effects of hepatic JNK deficiency.

Main Methods:

  • Generation of mice with selective ablation of the Fgf21 gene in hepatocytes.
  • Assessment of metabolic parameters, including blood glucose concentration, glucose intolerance, and insulin intolerance.
  • Analysis of hepatic FGF21 expression regulation by JNK during fasting/feeding cycles.

Main Results:

  • Hepatocyte-specific FGF21 deficiency led to a significant reduction in circulating FGF21 levels.
  • The protective metabolic benefits of hepatic JNK deficiency were abolished in mice lacking hepatocyte FGF21.
  • JNK signaling was shown to regulate hepatic FGF21 expression in response to fasting and feeding.

Conclusions:

  • Hepatokine FGF21 is a critical mediator of JNK-regulated metabolic syndrome.
  • Targeting the JNK-FGF21 axis in hepatocytes may offer therapeutic strategies for metabolic disorders.
  • FGF21 plays a key role in the liver's response to JNK signaling in the context of metabolic regulation.

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