High fat diet influences T cell homeostasis and macrophage phenotype to maintain chronic inflammation

Abstract

Abstract Over the past 20 years obesity has become a global health problem affecting the life expectancy of people at epidemic proportions. Obesity is characterized as a state of low-grade chronic inflammation that influences the development and progression of many chronic diseases. A unique role of T cells in adipose tissue has been shown in the initiation and regulation of the inflammatory cascade. However, the mechanisms responsible for the obesity-associated inflammation are not known. We investigated how high fat diet may influence homeostatic expansion of T cells, macrophage behavior and inflammation. High fat diet consumption alters the body weight, fat mass, and lean mass of mice when compared with those on a normal diet. The high fat diet increases the frequency of CD44+ and TCR αβ+T cells in the epididymal adipose tissues as compared with a normal diet. In mice consuming a high fat diet, we also found a significant increase in the frequency of CXCR3+ activated CD8T cells, CD8+KLRG1 cells and pro-inflammatory cytokines in mucosal and epididymal adipose tissues. High fat diet consumption resulted in greater than 2 fold changes in 85 gene and 142 miRs in epididymal adipose immune cells. Among these, ten inflammatory, obesity miRNAs and genes were validated by RT-PCR analysis. Pathway analysis also validated that differentially regulated miRNAs and gene target mRNAs are associated with T cell homeostatic expansion and macrophage function. Taken together, these results indicate that high fat diet modulates T cell homeostatic proliferation, macrophage phenotype, inflammatory miRNAs and genes to sustain inflammation. This study supports a key role of T cell homeostasis and macrophages to induce inflammation during high fat diet-induced obesity.