School of Public Health, Soochow University, Suzhou, 215123, China.
The Fifth People's Hospital in Suzhou, 215007, Suzhou, China.
Food Chem Toxicol. 2022 Dec;170:113451. doi: 10.1016/j.fct.2022.113451. Epub 2022 Oct 2.
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.
铅（Pb）和肥胖是代谢紊乱的共同危险因素。然而，对于这两种压力源对代谢的联合影响仍缺乏研究。本研究使用 C57BL/6J 小鼠进行实验，将其暴露于 200mg/L Pb 或/和 HFD 中 24 周，以研究慢性 Pb 暴露对肥胖小鼠的影响及其潜在机制。结果表明，Pb 显著增加了体重、内脏肥胖、空腹血糖水平和胰岛素抵抗，并加重了 HFD 喂养小鼠的肝损伤、肝脂质蓄积和脂肪变性。进一步分析表明，Pb 显著抑制了胰岛素信号通路 PI3K/AKT 和脂肪酸β氧化，并加速了脂肪酸的合成。此外，Pb 加剧了 HFD 诱导的肠道微生物群落失调，表现为致病菌属如脱硫弧菌、阿里斯泰普斯菌和幽门螺杆菌的比例增加，而有益菌阿克曼氏菌和巴恩斯氏菌的比例降低，这些与肥胖呈负相关。这些结果表明，Pb 暴露可能通过破坏肠道微生物群落来加剧 HFD 小鼠肝脏糖脂代谢的紊乱。
