Prenatal exposure to PM2.5 disturbs the glucose metabolism of offspring fed with high-fat diet in a gender-dependent manner

Studies have shown that maternal exposure to PM_2.5 could potentially disrupt glucose and lipid metabolism in offspring supplied with high-fat diet, yet whether this effect is gender-dependent or not and the underlying biological mechanisms are not well understood. In our current research, female ICR mice were exposed to filtered air (FA) or concentrated ambient PM_2.5 (CAP) before and during pregnancy. The offspring mice were fed with control diet (CD) or high-fat diet (HFD) for 9 weeks, and their metabolic conditions were analyzed. Our findings reveal that maternal exposure to PM_2.5 induced glucose intolerance and insulin resistance in female offspring fed with HFD but not in males. Specifically, hepatic insulin resistance as indicated by significantly decreased AKT phosphorylation (p-AKT) level, changed liver structure as indicated by increased ballooning and steatosis based on H&E staining images, and impaired liver function as indicated by up-regulated ALT activity were observed in HFD-fed female offspring from CAP-exposed mothers in comparison to those from FA-exposed ones. Further analysis indicated that these impacts of prenatal PM_2.5 exposure on glucose metabolism in offspring may result from disturbed gluconeogenesis and induced inflammatory response in liver. Our research underscores that prenatal PM_2.5 exposure induces glucose metabolism abnormalities in offspring fed with HFD in a gender-dependent manner, and the liver potentially serves as a key player in mediating these effects of maternal PM_2.5 exposure.