Tea polyphenols ameliorates insulin resistance and inflammation by modulating macrophage polarization via JAK2/STAT3 pathway in aged T2DM combined with NAFLD rats

Macrophages are the key cells of liver inflammation-immune regulation in a dynamic polarized state, which can differentiate into pro-inflammatory M1-like and anti-inflammatory M2-like in response to different micro-environmental signals. Insulin resistance (IR) and inflammation induced by the increased M1-like macrophages and decreased M2-like macrophages is a key component in the progression of aged type 2 diabetes mellitus (T2DM) combined with nonalcoholic fatty liver disease (NAFLD) and have become a new target for regulating glycolipid metabolism in recent years. In this study, we found that tea polyphenols (TP) can improve aged T2DM combined with NAFLD by modulating macrophage polarization in liver. More specifically, we have further demonstrated that TP promotes M2-like macrophages by activating the JAK2/STAT3 signaling pathway, and then protects the liver injury exacerbated by IR and inflammation. The results of this study can provide new ideas for the prevention and treatment of aged T2DM combined with NAFLD. • TP protects the liver from damage caused by IR and inflammation in aged T2DM combined with NAFLD rats. • Activating M2-like macrophage polarization inhibits IR and inflammation, promoting recovery from liver injury and steatosis. • TP activates the M2-like polarization of macrophages via the JAK2/STAT3 signaling pathway.