Short Term High Fat Diet Challenge Promotes Alternative Macrophage Polarization in Adipose Tissue via Natural Killer T Cells and Interleukin-4

Abstract

Background: 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. Conclusion: NKT cells in adipose tissue play important role in linking acute HFD feeding with adipose inflammation. Significance: Acute HFD feeding is unexpectedly associated with pronounced and dynamic immune responses in adipose tissue.

A short bout of HFD promotes long-lasting hepatic lipid accumulation

“…The finding of similar body weight after a short-bout of HFD is in line with some 5,17,18 but not all studies [1][2][3][4] examining the effect of short-term HFD on metabolism in mice. Possibly, differences in dietary composition, housing conditions, genetic background or age at dietary intervention may have contributed to observed differences in body weight gain.…”

“…[2][3][4] Here, we provide evidence that such alterations may persist after switching to a standard rodent diet. Accordingly, a recovery feeding period with a chow diet 8 times longer than the HFD exposure did not fully normalize glucose tolerance.…”

“…1,2,4,5 It was previously suggested that such rise in TNFa may be responsible for observed hepatic derangements induced by short-term HFD. 1 As depicted in Figure 2A, TNFa expression in mesenteric WAT was »4-fold higher in HFD RF mice compared to solely chow-fed littermates.…”

“…[1][2][3][4][5] While glucose intolerance mainly results from impaired hepatic insulin sensitivity, increased hepatic fat accumulation upon short-term HFD may evolve due to elevated circulating free fatty acid (FFA) levels provoked by dietary fat supply. 1,3,5,6 Likewise, plasma FFA were shown to be the main source of fatty acids bound in liver triglycerides in manifested obesity.…”

Adipokines and insulin action

“…While previously white adipose tissue (WAT) was regarded as a passive site for energy storage, identification of WAT secreted factors and their signaling effects on various tissues implicate a role for adipose in whole body glucose and lipid metabolism, insulin action, hemostasis, reproduction, and immunity. [8][9][10][11][12][13][14] These factors of hormones and cytokines, collectively coined "adipokines" due to their secretory and signaling nature, derive from either adipocytes or the stromal vascular cells within the adipose tissue matrix, including preadipocytes, fibroblasts, and macrophages. 10,15 The diverse systemic functions of adipose tissue are likely to be mediated by adipokines.…”