Regulatory T cells differentiation in visceral adipose tissues contributes to insulin resistance by regulating JAZF‐1/PPAR‐γ pathway

Abstract

AbstractRegulatory T cell (Treg) activity and differentiation in visceral adipose tissue (VAT) play an important role in inhibiting chronic inflammation and insulin resistance. Whether JAZF‐1 and PPAR‐γ mediate VAT Treg differentiation to promote the inhibition of chronic inflammation and insulin resistance remains unclear. Here, we investigated the roles of JAZF‐1 and PPAR‐γ in VAT Treg differentiation, inflammation and insulin resistance using a transgenic mouse model. First, we determined that the levels of glucose and insulin biochemical markers in the JAZF‐1 transgenic general feeding or high‐fat groups were lower than those in the wild‐type general feeding or high‐fat groups. Second, the levels of CD4+, CD25+, and FOXP3+ differentiation markers in the JAZF‐1 transgenic general feeding or high‐fat groups were significantly higher than those in the wild‐type groups. PPAR‐γ inhibition was associated with low levels of CD4+, CD25+ and FOXP3+ differentiation markers. Third, the levels of TNF‐α, IL‐1β and IL‐6 in the JAZF‐1 transgenic groups were lower than those in the wild‐type groups, whereas IL‐10 and TGF‐β levels were higher in the JAZF‐1 transgenic groups than in the wild‐type groups. After using the PPAR‐γ inhibitor, we observed that TNF‐α, IL‐1β and IL‐6 increased, while IL‐10 and TGF‐β decreased. We found that JAZF‐1 and PPAR‐γ could promote Tregs differentiation and regulate insulin resistance by synergistically decreasing the expression levels of TNF‐α, IL‐1β and IL‐6 and increasing those of IL‐10 and TGF‐β.