Abstract
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.
Highlights
Our understanding of immune responses at early stages of obesity is very limited
We show that an acute high fat diet (HFD) challenge is unexpectedly associated with elevated alternative (M2) macrophage polarization in adipose tissue mediated by Natural Killer T (NKT) cells
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
Summary
Our understanding of immune responses at early stages of obesity is very limited. Results: Acute HFD feeding promotes alternative macrophage polarization in adipose tissue via NKT cells and IL-4. Data show that expanding adipose tissue attracts immune cells and releases cytokines that may cause insulin resistance, disrupt lipid metabolism, and promote atherosclerosis [1,2,3] Despite these advances, a comprehensive picture of inflammation, at the initiation and resolution stages in adi-. A better delineation of the events associated with the early stages or onset of obesity may help understand the often-irreversible changes that take place at the established phase of obesity, and may reveal the interplay between metabolic and immune systems when challenged with a new diet highly enriched in lipids. We recently showed that the activation of NKT cells by ␣GalCer promotes M2 macrophage polarization in adipose tissue and improves systemic glucose homeostasis at different stages of obesity [27]. We show that short-term 4d HFD feeding unexpectedly promotes M2 macrophage polarization and arginase 1 expression in adipose tissue; and strikingly, this effect is mediated by NKT cells, in part via IL-4
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
