Quercetin improves the adipose inflammatory response and insulin signaling to reduce "real-world" particulate matter-induced insulin resistance

Abstract

Numerous epidemiological data and experimental studies support a strong link between fine particulate matter (less than 2.5 mm in aerodynamic diameter, PM_2.5) exposure and the development of insulin resistance/type 2 diabetes mellitus (T2DM). Quercetin (Que), a flavonoid compound with anti-inflammatory effects, has been confirmed to improve glucose metabolic disorders in rodents and humans. In this study, we investigated the underlying mechanisms of particulate matter (PM)-induced glucose metabolic disorder and subsequently examined the protective effect and mechanism of quercetin supplementation. Male C57BL/6 mice in the control group and PM group were exposed to ambient filtered air (FA) or PM (6 h/day, 7 days/week) for 18 weeks. Mice in the Que group were exposed to PM for 18 weeks and administered Que (50 or 100 mg/kg bw). Glucose tolerance, insulin sensitivity, and systemic and visceral white adipose tissue (vWAT) inflammatory responses were measured. The expression of proteins involved in insulin signal transduction in vWAT was assessed. Chronic PM exposure caused systemic and vWAT inflammation characterized by an increase in serum IL-6 and TNF-α levels and increased vWAT macrophage filtration, triggering NLRP3 inflammasome activation, impairing the classic glucose metabolism signal in vWAT, and inducing whole-body insulin resistance. Moreover, Que administration significantly alleviated systemic and vWAT inflammation, abolished NLRP3 inflammasome activation, and improved signaling abnormalities characteristic of insulin resistance in vWAT and adipocytes. Based on these findings, chronic PM exposure activated the NLRP3 inflammasome and subsequently caused systemic and WAT inflammation and impaired insulin signaling in vWAT and adipocytes. Most importantly, Que administration inhibited NLRP3 inflammasome-mediated inflammation and insulin signaling in vWAT to improve these adverse effects.

Keywords: Inflammation; Insulin resistance; NLRP3 inflammasome; Particulate matter; Quercetin; Visceral adipose tissue.