Aerobic endurance training improves nonalcoholic fatty liver disease (NAFLD) features via miR-33 dependent autophagy induction in high fat diet fed mice
Aerobic endurance training improves nonalcoholic fatty liver disease (NAFLD) features via miR-33 dependent autophagy induction in high fat diet fed mice
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DOI：
10.1016/j.orcp.2017.01.004
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发表时间：
2018-01-01
影响因子：
4.3
通讯作者：
Gorgani-Firuzjaee, Sattar
中科院分区：
文献类型：
--
作者：
Ghareghani, Parvin;Shanaki, Mehrnoosh;Gorgani-Firuzjaee, Sattar
由于生活方式的改变，肥胖及其相关并发症如胰岛素抵抗、2型糖尿病和非酒精性脂肪肝引起了世界范围的健康问题。经常运动是对抗肥胖代谢并发症的常用处方，但其分子机制尚未完全阐明。本研究从miR-33的表达和自噬途径两个方面探讨了运动训练对高脂饮食小鼠降脂作用的分子机制。24只小鼠被分配到正常食物（NC）（n =8）、高脂饮食（HFD）（n =16）组，并经受NC和HFD 13周。HFD组又分为安静组（HFD组，n =8）和持续耐力训练组（HFD + CET组，n =8）。HFD + CET小鼠在23周的HFD疗程中进行10周的跑台跑步。HFD可增加体重、空腹血糖、甘油三酯、胆固醇、谷草转氨酶（AST）、丙氨酸转氨酶（ALT）、肝脏脂肪生成基因表达，降低miR-33 mRNA表达和自噬途径，而训练可逆转这些变化。外源性miR-33模拟序列诱导HepG 2细胞自噬并减少脂肪生成。在HepG 2细胞中，雷帕霉素诱导的自噬减少脂肪生成，氯喹抑制自噬，增强脂肪生成。这些发现表明，有氧运动训练作为一种非药物疗法，通过miR-33依赖性自噬诱导发挥其降脂作用。(C)2017年亚洲大洋洲肥胖研究协会。由爱思唯尔有限公司出版。保留所有权利。
Due to changes in life style, obesity and obesity related complication such as insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease caused worldwide health problems. Regular exercise has been frequently prescribed to combat metabolic complication of obesity but its molecular mechanism has not been fully illustrated. We investigated molecular mechanism of lipid lowering effect of exercise training in high fat diet fed mice by focusing on miR-33 expression and autophagy pathway. 24 mice were assigned to normal chow (NC) (n =8), high-fat diet (HFD) (n =16) group and subjected to NC and HFD for 13-weeks. HFD groups were divided to sedentary (HFD n =8) or continuous endurance training (HFD + CET, n =8) subgroups. The HFD + CET mice were subjected to treadmill running for 10-weeks in 23-week HFD course. HFD increased body weight, fasting blood sugar, triglyceride, cholesterol, aspartate aminotransferase (AST), alanine aminotransferase (ALT), liver lipogenic genes expression and reduced miR-33 mRNA expression and autopahgy pathway while training program reversed them. Exogenous miR-33 mimic sequence induced autophagy and reduced lipogenesis in HepG2 cells. Autophagy induction by rapamycin reduced lipogenesis and autophagy inhibition by chloroquine, enhanced lipogenesis in HepG2 cells. These findings suggest that aerobic exercise training as a non-pharmacological therapy exerts its lipid lowering effects by miR-33 dependent autophagy induction. (C) 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.