Gu Xueyan, Ma Xiaocui, Mo Limin, Wang Qiyu
Department of Sports and Nutrition, Kunsan National University, Gunsan, Korea; Research Institute of Microbiology, Jiangxi Academy of Sciences, Nanchang, China.
Henan Key Laboratory of Pediatric Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Chin J Physiol. 2022 Nov-Dec;65(6):301-310. doi: 10.4103/0304-4920.365461.
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is often caused by obesity. Currently, moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) are two effective treatments for reducing fat mass in patients with obesity and NAFLD. However, the comparative fat-reducing effects and underlying molecular mechanisms of MICT and HIIT remain unclear. This comprehensive study was performed on male Wistar rats treated with standard diet, high-fat diet, MICT, and HIIT to explore their comparative fat-reducing effects and corresponding molecular mechanisms. HIIT had a greater effect on hepatic vacuolation density and lipid content reduction than MICT, and triglyceride and total cholesterol levels in the serum and the liver demonstrated different sensitivities to different exercise training programs. At the molecular level, both MICT and HIIT altered the processes of fatty acid synthesis, fatty acid transport, fatty acid β-oxidation, and cholesterol synthesis, wherein the transcriptional and translational levels of signaling molecules peroxisome proliferator-activated receptors (PPARs) regulating fatty acid and cholesterol synthesis were strongly changed. Moreover, the metabolic pathways of amino acids, bile acids, and carbohydrates were also affected according to transcriptome analysis, and the changes in the above-mentioned processes in the HIIT group were greater than those in the MICT group. In combination with the search tool for the retrieval of interacting genes/proteins (STRING) analysis and the role of PPARs in lipid metabolism, as well as the expression pattern of PPARs in the MICT and HIIT groups, the MICT-and HIIT-induced fat loss was mediated by the PPAR pathway, causing feedback responses in fatty acid, steroid, amino acid, bile acid, and carbohydrate metabolism, and HIIT had a better fat-reducing effect, which may be initiated by PPAR-α. This study provides a theoretical basis for targeted therapy of patients with obesity and NAFLD.
非酒精性脂肪性肝病(NAFLD)是最常见的慢性肝病,通常由肥胖引起。目前,中等强度持续训练(MICT)和高强度间歇训练(HIIT)是减轻肥胖和NAFLD患者脂肪量的两种有效治疗方法。然而,MICT和HIIT的比较减脂效果及潜在分子机制仍不清楚。本综合研究对接受标准饮食、高脂饮食、MICT和HIIT治疗的雄性Wistar大鼠进行,以探讨它们的比较减脂效果及相应分子机制。与MICT相比,HIIT对肝脏空泡化密度和脂质含量降低的作用更大,血清和肝脏中的甘油三酯和总胆固醇水平对不同运动训练方案表现出不同的敏感性。在分子水平上,MICT和HIIT均改变了脂肪酸合成、脂肪酸转运、脂肪酸β-氧化和胆固醇合成过程,其中调节脂肪酸和胆固醇合成的信号分子过氧化物酶体增殖物激活受体(PPARs)的转录和翻译水平发生了强烈变化。此外,根据转录组分析,氨基酸、胆汁酸和碳水化合物的代谢途径也受到影响,HIIT组上述过程的变化大于MICT组。结合检索相互作用基因/蛋白质的搜索工具(STRING)分析、PPARs在脂质代谢中的作用以及PPARs在MICT和HIIT组中的表达模式,MICT和HIIT诱导的脂肪减少是由PPAR途径介导的,在脂肪酸、类固醇、氨基酸、胆汁酸和碳水化合物代谢中引起反馈反应,且HIIT具有更好的减脂效果,这可能由PPAR-α启动。本研究为肥胖和NAFLD患者的靶向治疗提供了理论依据。