Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China; The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, Gansu, China.
Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China.
Mol Cell Endocrinol. 2024 Nov 1;593:112337. doi: 10.1016/j.mce.2024.112337. Epub 2024 Aug 2.
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide; however, effective intervention strategies for NAFLD are still unavailable. The present study sought to investigate the efficacy of chiglitazar, a pan-PPAR agonist, in protecting against NAFLD in mice and its underlying molecular mechanism. Male C57BL/6 J mice were fed a high-fat diet (HFD) for 8 weeks to generate NAFLD and the HFD was continued for an additional 10 weeks in the absence or presence of 5 mg/kg/d or 10 mg/kg/d chiglitazar by gavage. Chiglitazar significantly improved dyslipidemia and insulin resistance, ameliorated hepatic steatosis and reduced liver inflammation and oxidative stress in NAFLD mice. RNA-seq revealed that chiglitazar alleviated HFD-induced NAFLD in mice through multiple pathways, including fatty acid metabolism regulation, insulin signaling pathway, and AMPK signaling pathway. This study demonstrated the potential therapeutic effect of chiglitazar on NAFLD. Chiglitazar ameliorated NAFLD by modulating multiple pathways.
非酒精性脂肪性肝病（NAFLD）是全球最常见的慢性肝病之一；然而，NAFLD 的有效干预策略仍然缺乏。本研究旨在探讨全过氧化物酶体增殖物激活受体（PPAR）激动剂曲格列酮对保护小鼠 NAFLD 的疗效及其潜在的分子机制。雄性 C57BL/6J 小鼠喂食高脂肪饮食（HFD）8 周以产生 NAFLD，并在不给予或给予 5mg/kg/d 或 10mg/kg/d 曲格列酮灌胃的情况下继续喂食 HFD 10 周。曲格列酮显著改善了 NAFLD 小鼠的血脂异常和胰岛素抵抗，改善了肝脂肪变性，减轻了肝脏炎症和氧化应激。RNA-seq 显示，曲格列酮通过多种途径缓解了 HFD 诱导的小鼠 NAFLD，包括脂肪酸代谢调节、胰岛素信号通路和 AMP 激活蛋白激酶（AMPK）信号通路。本研究表明曲格列酮对 NAFLD 具有潜在的治疗作用。曲格列酮通过调节多种途径改善 NAFLD。
