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Updated: Jan 10, 2026

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
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Rab2A modulates liver fibroblast growth factor 21 (FGF21) expression and systemic metabolism via apolipoprotein

Zi-Yue Chen1, Min Xu2, Shuai Chen1

  • 1State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, School of Medicine, Nanjing University, Nanjing, China.

The Journal of Biological Chemistry
|November 28, 2025
PubMed

Insights

A novel pathway regulating Fibroblast Growth Factor 21 (FGF21) involves Rab2A, apolipoprotein B (APOB), and cAMP-responsive element-binding protein H (CREBH). This axis impacts obesity and systemic metabolism.

Area of Science:

  • Metabolic regulation
  • Hepatology
  • Molecular endocrinology

Background:

  • Fibroblast growth factor 21 (FGF21) is a key hepatokine regulating systemic metabolism.
  • Previous studies linked liver-specific Rab2A deficiency to impaired VLDL lipidation and APOB accumulation.

Purpose of the Study:

  • To elucidate a novel regulatory pathway for FGF21 involving the small GTPase Rab2A.
  • To investigate the role of APOB and CREBH in mediating FGF21 regulation.

Main Methods:

  • Utilized mouse models with liver-specific Rab2A deficiency.
  • Administered high-fat diets to induce obesity.
  • Employed adenovirus-mediated knockdown of CREBH and APOB.
  • Measured circulating FGF21 levels and assessed metabolic phenotypes.

Main Results:

  • Hepatic Rab2A inhibition protected mice from high-fat diet-induced obesity.
  • This protection was associated with significantly elevated circulating FGF21 levels.
  • Adenovirus-mediated knockdown of CREBH or APOB largely rescued the FGF21 elevation and protective phenotype.

Conclusions:

  • A novel Rab2A-APOB-CREBH signaling axis is identified in the liver.
  • This pathway plays a crucial role in the hepatic regulation of FGF21.
  • Targeting this axis may offer therapeutic strategies for metabolic disorders.
Keywords:
AMPKCREBHFGF21Rab2AVLDLnutrient sensing

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