Hunan Provincial Key Laboratory of Physical Fitness and Sports Rehabilitation, Hunan Normal University, Changsha 410012, China.
Yangtze University, College of Arts and Sciences, Jingzhou 434020, China.
Food Funct. 2024 Sep 30;15(19):9796-9812. doi: 10.1039/d4fo02984d.
Fat is a "double-edged sword": while it is a necessary substance for the body, the long-term intake of excessive fat will cause obesity, with the liver subjected to lipotoxicity as it accumulates. It will then continue to deteriorate, eventually leading to liver failure, which is a negative impact of high-fat food intake. Research has shown that exercise can reverse the side effects of a chronic high-fat diet and help the body to mitigate the harmful effects of lipotoxicity. In our study, it was found that moderate-intensity cardio-training (MICT) and high-intensity interval exercise (HIIT) effectively protected the livers of high-fat diet (HFD) ApoE mice against lipotoxicity. Previous results demonstrated that 12 weeks of HFD resulted in a significant elevation of CD36 in the livers of C57BL/6J mice, while knockdown of CD36 did not reduce the accumulation of fat in the liver. Therefore, we used ApoE mice as experimental subjects. Although HFD caused the development of hyperlipidemia and atherosclerosis, it is interesting to note that, due to the knockdown of ApoE, the livers of ApoE mice in the non-exercise group did not show significant lipid deposition; however, after 12 weeks of MICT and HIIT, the livers of ApoE mice showed significant lipid deposition. After we analyzed the lipid metabolism in their livers, we found that this was caused by the promotion of transport of peripheral fat into the liver due to exercise. Moreover, 12 weeks of exercise effectively reduced atherosclerosis, and the livers of ApoE mice in the exercise group were not damaged by lipotoxicity. The results showed that a 12-week exercise treatment activated AMPK in the livers of HFD ApoE mice through the APN-AdipoR1 signaling pathway, improved hepatic lipid metabolism disorders, and promoted the nuclear translocation of TFEB to enhance autophagic-lysosomal lipid scavenging. After the peripheral lipid is input into the liver due to exercise, the energy generated through gluconeogenesis can be used to replenish the energy consumed by exercise and maintain the normal operation of various functions in the liver, based on which the high autophagic flux in the liver can be maintained and the lipid clearance rate can be enhanced to protect the liver from lipotoxicity.
脂肪是一把“双刃剑”：它是身体必需的物质，但长期摄入过多的脂肪会导致肥胖，肝脏会因脂肪堆积而受到脂毒性。随后肝脏会持续恶化，最终导致肝功能衰竭，这是高脂食物摄入的负面影响。研究表明，运动可以逆转慢性高脂肪饮食的副作用，帮助身体减轻脂毒性的有害影响。在我们的研究中，发现中等强度有氧运动（MICT）和高强度间歇运动（HIIT）可有效保护高脂肪饮食（HFD）ApoE 小鼠的肝脏免受脂毒性。先前的结果表明，12 周的 HFD 可显著提高 C57BL/6J 小鼠肝脏中的 CD36，而敲低 CD36 并不能减少肝脏中脂肪的堆积。因此，我们使用 ApoE 小鼠作为实验对象。尽管 HFD 导致高脂血症和动脉粥样硬化的发生，但有趣的是，由于 ApoE 的敲低，非运动组 ApoE 小鼠的肝脏并没有明显的脂质沉积；然而，经过 12 周的 MICT 和 HIIT 后，ApoE 小鼠的肝脏出现了明显的脂质沉积。在分析了它们肝脏中的脂质代谢后，我们发现这是由于运动促进了外周脂肪向肝脏的转运。此外，12 周的运动可有效减轻动脉粥样硬化，运动组 ApoE 小鼠的肝脏不受脂毒性的损害。结果表明，12 周的运动通过 APN-AdipoR1 信号通路激活了 HFD ApoE 小鼠肝脏中的 AMPK，改善了肝脏脂质代谢紊乱，促进了 TFEB 的核转位，增强了自噬溶酶体脂质清除。运动后外周脂肪进入肝脏，通过糖异生产生的能量可以用来补充运动消耗的能量，维持肝脏各种功能的正常运转，从而维持肝脏中高自噬流，增强脂质清除率，保护肝脏免受脂毒性。
