Short term high fat diet challenge promotes alternative macrophage polarization in adipose tissue via natural killer T cells and interleukin-4.
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.
Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853, USA.
Yewei
Y
Ji
Shengyi
S
Sun
Sheng
S
Xia
Liu
L
Yang
Xiaoqing
X
Li
Ling
L
Qi
D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000166:cytology* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects
D015847:Interleukin-4