Protective Effect of Luteolin on Inflammatory Factor‐Mediated Insulin Resistance in 3T3‐L1 Adipocytes

Abstract

Obesity and insulin resistance have been recently linked to a low‐grade chronic inflammatory response characterized by increased macrophage infiltration, altered cytokine production, and activation of inflammatory signaling pathway in adipose tissue. Pharmacological agents and natural products capable of reducing inflammatory activity possess anti‐diabetic properties. Luteolin, a naturally occurring flavonoid, has been demonstrated to inhibit LPS‐induced TNFα release and activation of NF‐κB pathway in macrophages. However, little is known about the role and mechanism of luteolin on anti‐insulin resistance and diabetes. In this study, we investigated the role of luteolin in the regulation of inflammatory factor‐mediated insulin resistance in 3T3‐L1 adipocytes. Here we show that luteolin treatment for 24 hrs increased insulin‐stimulated glucose uptake in a dose‐dependent manner in 3T3‐L1 adipocytes. Our results also demonstrated that 24 hour treatment of luteolin enhanced insulin‐stimulated PPARγ expression in 3T3‐L1 adipocytes. Interestingly, time‐dependent serine phosphorylation of insulin receptor substrate 1 (IRS‐1) by TNFα was blocked in 3T3‐L1 adipocytes with pretreatment of luteolin for 30 min. Furthermore, luteolin treatment for 24 hrs attenuated LPS‐stimulated TNF‐α secretion from both 3T3‐L1 preadipocytes and adipocytes. When added to 3T3‐L1 cells together with LPS during the entire differentiation process, luteolin antagonized the effect of LPS on the induction of IL‐6 gene expression in 3T3‐L1 adipocytes. Thus, our data demonstrate that luteolin plays a protective role in inflammation‐mediated adipocyte dysfunction and insulin resistance.