Fibroblast growth factor 21 reverses suppression of adiponectin expression via inhibiting endoplasmic reticulum stress in adipose tissue of obese mice

Exp Biol Med (Maywood). 2017 Feb;242(4):441-447. doi: 10.1177/1535370216677354. Epub 2016 Nov 5.

Abstract

Fibroblast growth factor 21 (FGF21) has recently emerged as a novel endocrine hormone involved in the regulation of glucose and lipid metabolism. However, the exact mechanisms whereby FGF21 mediates insulin sensitivity remain not fully understood. In the present study, FGF21was administrated in high-fat diet-induced obese mice and tunicamycin-induced 3T3-L1 adipocytes, and metabolic parameters, endoplasmic reticulum (ER) stress indicators, and insulin signaling molecular were assessed by Western blotting. The administration of FGF21 in obese mice reduced body weight, blood glucose and serum insulin, and increased insulin sensitivity, resulting in alleviation of insulin resistance. Meanwhile, FGF21 treatment reversed suppression of adiponectin expression and restored insulin signaling via inhibiting ER stress in adipose tissue of obese mice. Additionally, suppression of ER stress via the ER stress inhibitor tauroursodeoxycholic acid increased adiponectin expression and improved insulin resistance in obese mice and in tunicamycin-induced adipocytes. In conclusion, our results showed that the administration of FGF21 reversed suppression of adiponectin expression and restored insulin signaling via inhibiting ER stress under the condition of insulin resistance, demonstrating the causative role of ER stress in downregulating adiponectin levels.

Keywords: Adiponectin; endoplasmic reticulum stress; fibroblast growth factor 21; insulin resistance; obese mice; tauroursodeoxycholic acid.

MeSH terms

  • 3T3 Cells
  • Adipocytes / metabolism
  • Adiponectin / biosynthesis*
  • Adipose Tissue / metabolism*
  • Animals
  • Blood Glucose / drug effects
  • Cell Line
  • Diet, High-Fat
  • Endoplasmic Reticulum Stress / physiology*
  • Fibroblast Growth Factors / pharmacology*
  • Insulin Resistance / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Signal Transduction / drug effects
  • Taurochenodeoxycholic Acid / pharmacology
  • Tunicamycin / pharmacology

Substances

  • Adiponectin
  • Blood Glucose
  • fibroblast growth factor 21
  • Tunicamycin
  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine
  • Fibroblast Growth Factors