Short term high fat diet challenge promotes alternative macrophage polarization in adipose tissue via natural killer T cells and interleukin-4

J Biol Chem. 2012 Jul 13;287(29):24378-86. doi: 10.1074/jbc.M112.371807. Epub 2012 May 29.


Inflammation in adipose tissue plays an important role in the pathogenesis of obesity-associated complications. However, the detailed cellular events underlying the inflammatory changes at the onset of obesity have not been characterized. Here we show that an acute HFD challenge is unexpectedly associated with elevated alternative (M2) macrophage polarization in adipose tissue mediated by Natural Killer T (NKT) cells. Upon 4d HFD feeding, NKT cells are activated, promote M2 macrophage polarization and induce arginase 1 expression via interleukin (IL)-4 in adipose tissue, not in the liver. In NKT-deficient CD1d(-/-) mice, M2 macrophage polarization in adipose tissue is reduced while systemic glucose homeostasis and insulin tolerance are impaired upon 4d HFD challenge. Thus, our study demonstrate, for the first time to our knowledge, that acute HFD feeding is associated with remarkably pronounced and dynamic immune responses in adipose tissue, and adipose-resident NKT cells may link acute HFD feeding with inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Adipose Tissue, White / cytology
  • Adipose Tissue, White / drug effects
  • Animals
  • Blotting, Western
  • Cells, Cultured
  • Diet, High-Fat / adverse effects*
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism*
  • Macrophages / cytology*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Mice, Knockout
  • Natural Killer T-Cells / cytology*
  • Natural Killer T-Cells / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stromal Cells / cytology
  • Stromal Cells / drug effects


  • Interleukin-4