Curcumin protects against bisphenol A-induced hepatic steatosis by inhibiting cholesterol absorption and synthesis...

Curcumin is a polyphenol extracted from the rhizome of turmeric, and our previous research showed that curcumin inhibited cholesterol absorption and had cholesterol-lowering effect. Bisphenol A (BPA), a common plasticizer, is widely used in the manufacture of food packaging and is associated with non-alcoholic fatty liver disease (NAFLD). We hypothesized that curcumin could protect against BPA-induced hepatic steatosis by inhibiting cholesterol absorption and synthesis. Male CD-1 mice fed BPA-contaminated diet with or without curcumin for 24 weeks were used to test our hypothesis. We found that chronic low-dose BPA exposure significantly increased the levels of serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol and the contents of liver TG and TC, resulting in liver fat accumulation and hepatic steatosis while curcumin supplementation could alleviate BPA-induced dyslipidemia and hepatic steatosis. Moreover, the anti-steatosis and cholesterol-lowering effects of curcumin against BPA coincided with a significant reduction in intestinal cholesterol absorption and liver cholesterol synthesis, which was modulated by suppressing the expression of sterol regulatory element-binding protein-2 (SREBP-2), Niemann-Pick C1-like 1 (NPC1L1), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) in the small intestine and liver. In addition, the expression levels of liver lipogenic genes such as liver X receptor alpha (LXRα), SREBP-1c, acetyl-CoA carboxylase 1 (ACC1), and ACC2 were also markedly down-regulated by curcumin. Overall, our findings indicated that curcumin inhibited BPA-induced intestinal cholesterol absorption and liver cholesterol synthesis by suppressing SREBP-2, NPC1L1, and HMGCR expression, subsequently reducing liver cholesterol accumulation and fat synthesis, thereby preventing hepatic steatosis and NAFLD.