FGF9 inhibits browning program of white adipocytes and associates with human obesity

Yingkai Sun1, Rui Wang1, Shaoqian Zhao1

  • 1Department of Endocrinology and Metabolism, China National Research Center for Metabolic Diseases, Shanghai, China.

Insights

Fibroblast growth factor 9 (FGF9) inhibits white adipose tissue browning, a process crucial for combating obesity. FGF9

Area of Science:

  • Adipose tissue biology
  • Metabolic regulation
  • Obesity research

Background:

  • White adipose tissue browning is a therapeutic target for obesity.
  • Fibroblast growth factor 21 (FGF21) shows promise in treating obesity.
  • The role of other fibroblast growth factor (FGF) family members in adipose thermogenesis is largely unknown.

Purpose of the Study:

  • To investigate the role of FGF9 in adipose thermogenesis and obesity development.
  • To explore the molecular mechanisms underlying FGF9's effects on white adipocytes.

Main Methods:

  • Analysis of FGF family member mRNA expression in mouse adipose tissues.
  • In vitro studies on beige adipocyte differentiation from stromal vascular fraction (SVF).
  • FGF9 treatment, overexpression, and knockdown experiments.
  • RNA sequencing and real-time PCR to assess gene expression and pathway activation.

Main Results:

  • FGF9 is highly expressed in adipose tissue and decreases with cold stress.
  • FGF9 inhibits thermogenic gene expression during beige adipocyte differentiation.
  • FGF9 knockdown enhances thermogenic gene expression.
  • FGF9 treatment upregulates the hypoxia-inducible factor (HIF) pathway.
  • FGF9 expression is elevated in obese human and mouse adipose tissue.

Conclusions:

  • Adipose-derived FGF9 plays an inhibitory role in white adipocyte browning.
  • FGF9's anti-thermogenic effect may involve the activation of hypoxia signaling during early adipose browning.

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