Exercise in mice ameliorates high-fat diet-induced nonalcoholic fatty liver disease by lowering HMGCS2.
Exercise in mice ameliorates high-fat diet-induced nonalcoholic fatty liver disease by lowering HMGCS2.
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小鼠运动通过降低 HMGCS2 改善高脂饮食诱发的非酒精性脂肪肝
DOI：
10.18632/aging.202717
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发表时间：
2021-03-01
期刊：
影响因子：
--
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Qian X;Wang T;Gong J;Wang L;Chen X;Lin H;Tu W;Jiang S;Li S
非酒精性脂肪性肝病（NAFLD）是一种常见的慢性肝病。运动是预防NAFLD的治疗策略。然而，通过运动可以改善NAFLD的潜在分子机制仍然不清楚。本研究探讨了运动抑制小鼠高脂饮食（HFD）诱导的NAFLD发展的机制。雄性6周龄C57 BL/6 J小鼠喂食正常饮食或HFD 12周，然后诱导游泳或保持久坐不动8周。组织形态学，炎症因子，脂肪代谢酶，纤维化，脂肪变性，在HFD喂养的小鼠肝脏进行了测定，并在相关途径中的肝酶和分子的水平进行了分析。NAFLD小鼠表现出明显的脂肪变性、纤维化和肝损伤，以及肝脏中HMGCS 2、Wnt 3a/ β-连环蛋白和磷酸化（p）-AMPK的表达增加。运动显著减轻了这些症状，并下调了脂毒性肝组织中Wnt 3a/β-catenin的水平。在棕榈酸处理的HepG 2中，HMGCS 2表达的抑制降低了Wnt 3a/β-catenin途径的活化，并降低了p-AMPK。我们的研究结果表明，运动可以预防NAFLD相关的肝损伤，脂肪变性和纤维化。通过阻断HMGCS 2的上调和减弱Wnt 3a/β-catenin通路，部分实现了肝切除介导的肝保护作用。
Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. Exercise is a therapeutic strategy for preventing NAFLD. However, the underlying molecular mechanisms by which NAFLD can be ameliorated through exercise are still not clear. This study investigates the mechanisms by which exercise suppresses NAFLD development induced by a high-fat diet (HFD) in mice. Male 6-week-old C57BL/6J mice were fed a normal diet or HFD for 12 weeks and then induced to swim or remain sedentary for 8 weeks. Histomorphology, inflammatory factors, fat metabolizing enzymes, fibrosis, and steatosis were determined in HFD-fed mouse liver, and levels of hepatic enzymes and molecules in the related pathways were analyzed. NAFLD mice showed evident steatosis, fibrosis, and liver injury, and an increased expression of HMGCS2, Wnt3a/ β-catenin, and phosphorylated (p)-AMPK in the liver. Exercise significantly attenuated these symptoms and downregulated the level of Wnt3a/β-catenin in lipotoxic liver tissue. Inhibition of HMGCS2 expression decreased the activation of the Wnt3a/β-catenin pathway and lowered p-AMPK in palmitate-treated HepG2. Our results suggest that exercise prevents NAFLD-associated liver injury, steatosis, and fibrosis. Exercise-mediated hepatoprotection was achieved partly via the blocking of the upregulation of HMGCS2 and the attenuation of the Wnt3a/β-catenin pathway.
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