Curcumin protects against bisphenol A‐induced hepatic steatosis by inhibiting cholesterol absorption and synthesis in CD‐1 mice

Abstract

AbstractCurcumin 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.