Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe^–/– mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

脂质代谢紊乱会导致高脂血症和肝脂肪变性。开发同时改善高脂血症和肝脂肪变性的药物是理想的。硝唑尼特是 FDA 批准的口服抗原虫药物，具有出色的药代动力学和安全性。我们发现硝唑尼特及其代谢物替唑尼特诱导温和的线粒体解偶联并随后在 HepG2 细胞中激活 AMPK。硝唑尼特灌胃给药可抑制高脂饮食 (HFD) 引起的肝重、血液和肝脏脂质增加，并改善 HFD 引起的仓鼠肾脏脂质积累。硝唑尼特显着改善了 HFD 引起的仓鼠肝脏组织病理学变化。在已存在高脂血症和肝脂肪变性的仓鼠中，硝唑尼特也显示出治疗效果。Apoe ^–/–老鼠。本研究表明，将硝唑尼特重新用作治疗高脂血症和肝脂肪变性的药物是有希望的。