Fibroblast Growth Factor 21 Exerts its Anti-inflammatory Effects on Multiple Cell Types of Adipose Tissue in Obesity

Obesity (Silver Spring). 2019 Mar;27(3):399-408. doi: 10.1002/oby.22376. Epub 2019 Jan 31.

Abstract

Objective: Obesity-related, chronic, low-grade inflammation has been identified as a key factor in the development of many metabolic diseases, such as type 2 diabetes and cardiovascular diseases. Adipocytes, preadipocytes, and macrophages have been implicated in initiating inflammation in adipose tissue. This study aims to investigate the effects of fibroblast growth factor-21 (FGF-21) on obesity-related inflammation and its mechanisms in vivo and in vitro.

Methods: Monosodium glutamate (MSG) was used to induce obesity in mice and subsequently treated the mice with or without FGF-21. Primary adipocytes and stromal vascular fraction cells were isolated from MSG-obesity mice for additional experiments.

Results: Results obtained by ELISA and real-time polymerase chain reaction showed that FGF-21 efficiently ameliorated obesity-related inflammation in MSG-obesity mice. This study demonstrated that preadipocytes and adipocytes responded to anti-inflammatory effects of FGF-21. In vitro, 3 T3-L1 preadipocytes lacking β-klotho did not respond to FGF-21 under glucose uptake. Interestingly, the treatment of 3 T3-L1 preadipocytes with FGF-21 significantly attenuated lipopolysaccharide-induced inflammatory response.

Conclusions: Our study showed that FGF-21-induced glucose uptake and FGF-21-related anti-inflammatory effects are mediated by different signaling pathways. Moreover, FGF-21 showed anti-inflammatory effects on preadipocytes; these effects are mediated by the fibroblast growth factor receptor substrate 2/ERK1/2 signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Fibroblast Growth Factors / pharmacology
  • Fibroblast Growth Factors / therapeutic use*
  • Humans
  • Inflammation / drug therapy*
  • Mice
  • Obesity / drug therapy*

Substances

  • Anti-Inflammatory Agents
  • fibroblast growth factor 21
  • Fibroblast Growth Factors