Curcumin protects against bisphenol A-induced hepatic steatosis by inhibiting cholesterol absorption and synthesis in CD-1 mice.
Curcumin protects against bisphenol A-induced hepatic steatosis by inhibiting cholesterol absorption and synthesis in CD-1 mice.
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DOI：
10.1002/fsn3.3468
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发表时间：
2023-09
影响因子：
3.9
通讯作者：
Feng D
中科院分区：
文献类型：
--
作者：
Hong T;Zou J;Yang J;Liu H;Cao Z;He Y;Feng D
姜黄素是从姜黄根茎中提取的多酚，我们以前的研究表明姜黄素抑制胆固醇吸收，具有降低胆固醇的作用。双酚A（BPA）是一种常见的增塑剂，广泛用于食品包装的制造，与非酒精性脂肪肝（NAFLD）有关。我们假设姜黄素可以通过抑制胆固醇的吸收和合成来预防BPA诱导的肝脏脂肪变性。雄性CD-1小鼠喂食BPA污染的饮食（含或不含姜黄素）24周，以检验我们的假设。我们发现，慢性低剂量BPA暴露显著增加血清甘油三酯（TG）、总胆固醇（TC）和低密度脂蛋白胆固醇水平以及肝脏TG和TC含量，导致肝脏脂肪蓄积和肝脏脂肪变性，而姜黄素补充可减轻BPA诱导的血脂异常和肝脏脂肪变性。此外，姜黄素对BPA的抗脂肪变性和降胆固醇作用与肠道胆固醇吸收和肝脏胆固醇合成的显著减少相一致，这是通过抑制小肠和肝脏中固醇调节元件结合蛋白-2（SREBP-2）、尼曼-匹克C1样1（NPC 1 L1）和3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）的表达来调节的。此外，姜黄素还显著下调了肝脏X受体α（LXRα）、SREBP-1c、乙酰辅酶A羧化酶1（ACC 1）和ACC 2等肝脏脂肪生成基因的表达水平。总的来说，我们的研究结果表明，姜黄素通过抑制SREBP-2，NPC 1 L1和HMGCR表达来抑制BPA诱导的肠道胆固醇吸收和肝脏胆固醇合成，随后减少肝脏胆固醇积累和脂肪合成，从而预防肝脏脂肪变性和NAFLD。姜黄素通过抑制固醇调节元件结合蛋白-2、尼曼-匹克C1样1和3-羟基-3-甲基戊二酰辅酶A还原酶的表达，抑制双酚A诱导的肠胆固醇吸收和肝脏胆固醇合成，从而改善双酚A诱导的雄性CD-1小鼠肝脏脂肪变性。
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. Curcumin inhibited bisphenol A‐induced intestinal cholesterol absorption and liver cholesterol synthesis by suppressing sterol regulatory element‐binding protein‐2, Niemann–Pick C1‐like 1, and 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase expression, thus ameliorating hepatic steatosis induced by bisphenol A in male CD‐1 mice.
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影响因子：
2
作者：
Li, Qingrong;Zhang, Hongmin;Feng, Dan
通讯作者：
Feng, Dan
影响因子：
3.6
作者：
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通讯作者：
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影响因子：
3.5
作者：
Geng, Shanshan;Wang, Shijia;Zhong, Caiyun
通讯作者：
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影响因子：
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作者：
Feng D;Ohlsson L;Duan RD
通讯作者：
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