Abstract
Compared to the innate immune system, the contribution of the adaptive immune response during obesity and insulin resistance is still not completely understood. Here we demonstrate that high fat diet (HFD) increases the frequencies of activated CD4+ and CD8+ T cells and frequencies of T cells positive for IFN-γ and IL-17 in the adipose tissue. The adipocyte-derived soluble factor adiponectin reduces IFN-γ and IL-17 positive CD4+ T cells from HFD mice and dampens the differentiation of naïve T cells into Th1 cells and Th17 cells. Adiponectin reduces Th17 cell differentiation and restrains glycolysis in an AMPK dependent fashion. Treatment with adult worm extracts of the rodent filarial nematode Litomosoides sigmodontis (LsAg) reduces adipose tissue Th1 and Th17 cell frequencies during HFD and increases adiponectin levels. Stimulation of T cells in the presence of adipocyte-conditioned media (ACM) from LsAg-treated mice reduces Th1 and Th17 frequencies and this effect was abolished when ACM was treated with an adiponectin neutralizing antibody. Collectively, these data reveal a novel role of adiponectin in controlling pro-inflammatory CD4+ T cells during obesity and suggest that the beneficial role of helminth infections and helminth-derived products on obesity and insulin resistance may be in part mediated by adiponectin.
Highlights
With 2 billion overweight or obese individuals reported globally in 2013, the incidence of obesity is escalating at an alarming rate [1]
high fat diet (HFD) mice fed for 12–16 weeks on a HFD showed a higher body weight, adipose tissue weight as well as impaired glucose and insulin tolerance compared to normal chow diet (NCD) mice (Supplementary Figures 1B–G)
Depleting macrophages and B cells at obesity onset was sufficient to mitigate CD8+ T cell inflammation, while CD4+ T cell inflammation was rather subject to regulation by the adipocyte secreted insulin sensitizer adiponectin
Summary
With 2 billion overweight or obese individuals reported globally in 2013, the incidence of obesity is escalating at an alarming rate [1]. There is a growing body of evidence linking innate immune cells in general and macrophages in particular to inflammation and insulin resistance [2]. Recent reports have identified T cells as key players of the adaptive immune system in orchestrating the inflammatory effects of macrophages and thereby promoting insulin resistance [5, 6]. During obesity, increased numbers of memory T cells occur in the adipose tissue [7] and depletion of T cells in general or from the adipose tissue has been shown to decrease adipose tissue inflammation in obese mice and to improve insulin resistance [7, 8]. In addition to conventional antigen presenting cells like macrophages, dendritic cells, and B cells, non-immune
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