Improving hyperglycemic effect of FGF-21 is associated with alleviating inflammatory state in diabetes

Int Immunopharmacol. 2018 Mar:56:301-309. doi: 10.1016/j.intimp.2018.01.048. Epub 2018 Feb 3.

Abstract

Type 2 diabetes mellitus (T2DM) is accompanied by abnormal glucose metabolism and low-grade chronic inflammation. Fibroblast growth factor 21 (FGF-21) is a novel metabolic regulator and can function as an endocrine hormone to regulate glucose and lipid metabolism. Recently, FGF-21 was found to have anti-inflammatory effect, to our knowledge, the effect of FGF-21 on inflammatory state in diabetes has not been elucidated. Here, we use db/db mice as a Type 2 diabetes model to determine whether FGF-21 alleviates inflammatory state while improves hyperglycemia. Our results demonstrated that FGF-21 not only showed potent long lasting hypoglycemic effect, but also demonstrated strong anti-inflammatory effect in the serum and white adipose tissue. Besides, in vitro experiments, insulin resistance (IR) was induced in 3T3-L1 adipocytes by treating with TNF-α. Our results showed that TNF-α impaired glucose metabolism of 3T3-L1 adipocytes but FGF-21 repressed gene expression of inflammatory factors caused by IR and consequently improved the glucose metabolism in 3T3-L1 adipocytes. Furthermore, FGF-21 ameliorated glucose uptake of TNF-α-induced IR in 3T3-L1 adipocytes by inhibiting NF-κB signaling pathway.

Keywords: 3T3-L1 adipocytes; FGF-21; Glucose uptake; Inflammation; NF-κB.

MeSH terms

  • Adipocytes / physiology*
  • Adipose Tissue, White / metabolism*
  • Animals
  • Cell Line
  • Diabetes Mellitus, Type 2 / metabolism*
  • Fibroblast Growth Factors / metabolism*
  • Glucose / metabolism*
  • Hyperglycemia
  • Inflammation / metabolism*
  • Insulin Resistance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • NF-kappa B / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Glucose