Fas mutation reduces obesity by increasing IL-4 and IL-10 expression and promoting white adipose tissue browning

Sci Rep. 2020 Jul 20;10(1):12001. doi: 10.1038/s41598-020-68971-7.


Brown adipose tissue generates heat via the mitochondrial uncoupling protein UCP1 to protect against obesity and hypothermia. Fas mutant MRL/lpr mice exhibit a significantly leaner phenotype compared to wild type MRL/MpJ mice. In this study, we evaluated the inflammatory cell population in the adipose tissue of MRL/lpr mice, which could potentially influence their lean phenotype. Furthermore, we compared beige fat activity between the MRL/MpJ and MRL/lpr mice. Fas mutation resulted in high body temperature, improved glucose tolerance, and decreased fat mass and adipocyte size. Fas mutation prevented high-fat diet-induced obesity and decreased the white adipose tissue M1:M2 ratio. When mice were fed a high-fat diet, UCP1, IL-4, IL-10, and tyrosine hydroxylase genes had significantly higher expression in Fas-mutant mice than in wild type mice. After a cold challenge, UCP1 expression and browning were also significantly higher in the Fas-mutant mice. In summary, Fas-mutant mice are resistant to high-fat diet-induced obesity due to increased IL-4 and IL-10 levels and the promotion of thermogenic protein activity and browning in their adipose tissues. STAT6 activation might contribute to M2 polarisation by increasing IL-4 and IL-10 levels while increases in M2 and tyrosine hydroxylase levels promote browning in response to Fas mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / metabolism*
  • Animals
  • Cholesterol / blood
  • Diet, High-Fat
  • Energy Metabolism
  • Epididymis / pathology
  • Glucose Tolerance Test
  • Glycerol / blood
  • Inflammation / genetics
  • Inflammation / pathology
  • Insulin / blood
  • Interleukin-10 / metabolism*
  • Interleukin-4 / metabolism*
  • Leptin / blood
  • Male
  • Mice
  • Mutation / genetics*
  • Obesity / blood
  • Obesity / genetics*
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Thermogenesis
  • fas Receptor / genetics*


  • Fas protein, mouse
  • Insulin
  • Leptin
  • RNA, Messenger
  • fas Receptor
  • Interleukin-10
  • Interleukin-4
  • Cholesterol
  • Glycerol