Cuiqing Liu
Hangzhou Normal University, China
Title: Toxicity beyond the lung: connecting PM2.5 and diabetes
Biography
Biography: Cuiqing Liu
Abstract
Epidemiologic and experimental studies indicate the toxicological effects of air pollution and support an association between fine ambient particulate matter <2.5µm (PM2.5) exposure and insulin resistance (IR) /Type II diabetes mellitus (Type II DM). We investigated the role of innate immune cell activation and hypothalamic inflammation in PM2.5-mediated diabetes development. Wild-type C57BL/6 and CCR2-/- male fed on high fat diet or KKay mice (a genetic diabetes model) were assigned to concentrated ambient PM2.5 or filtered air via a whole body exposure system. At the end of the experiments, mice were sacrificed and multiple methods were used to examine targets of interest. Firstly, PM2.5 exposure resulted in whole body IR and increased hepatic lipid accumulation in the liver which was attenuated in CCR2-/- mice by inhibiting SREBP1c mediated transcriptional programming and decreasing fatty acid uptake. Secondly, PM2.5 exposure reduced phosphorylation levels of AKT, AMPK in visceral adipose tissue (VAT) and enhanced adipose tissue macrophage infiltration which were restored by CCR2 deficiency. Thirdly, PM2.5 exposure inhibited energy metabolism including O2 consumption, CO2 production, respiratory exchanging ratio and heat generation in a genetically susceptible model of Type II DM. Fourthly, PM2.5 exposure led to increased hypothalamic IL-6, TNFα, and IKKβ mRNA expression and microglial/astrocyte reactivity. Finally, Central inhibition of IKKβ prevents PM2.5 mediated peripheral inflammation and exaggeration of type II diabetes. These results provide novel insights into how air pollution may mediate susceptibility to insulin resistance and Type II DM.