Chronic lead exposure exacerbates hepatic glucolipid metabolism disorder and gut microbiota dysbiosis in high-fat-diet mice

Lead (Pb) and obesity are co-occurring risk factors for metabolic disorders. However, there is still a lack of study on the combined effects of both stressors on metabolism. C57BL/6J mice were exposed to 200 mg/L Pb or/and HFD for 24 weeks and were used to investigate the effects and underlying mechanisms of chronic Pb exposure on obese mice. The results showed that Pb significantly increased body weight, visceral obesity, fasting blood glucose levels, and insulin resistance, and aggravated liver damage, hepatic lipid accumulation and steatosis in HFD-fed mice. Further analysis showed that Pb significantly inhibited insulin signaling pathway PI3K/AKT and fatty acid β-oxidation, and accelerated fatty acid synthesis. Moreover, Pb exacerbated HFD-induced disruption of gut microbiota homeostasis, manifested by increased proportions of pathogenic genera such as Desulfovibrio, Alistipes and Helicobacter, and decreased proportions of beneficial microbes Akkermansia and Barnesiella, which were negatively associated with obesity. These results indicated that Pb exposure exacerbated the disruption of liver glucolipid metabolism in HFD mice possibly by disrupting gut microbiota.