Division of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University- Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA, 17033, USA.
Department of Public Health Sciences, The Pennsylvania State University- Milton S. Hershey Medical Center, Hershey, PA, USA.
Dig Dis Sci. 2020 Nov;65(11):3238-3243. doi: 10.1007/s10620-020-06226-1. Epub 2020 Apr 1.
Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH), is a more severe type of NAFLD. Exercise improves NASH, by reversing steatosis, and may arrest fibrosis. However, the mechanisms underlying these interactions are unknown. AMP-activated protein kinase (AMPK) is a fuel-sensing enzyme that is activated by energy stress. Mammalian target of rapamycin in complex 1 (mTORC1) is a nutrient sensor that regulates protein synthesis. In NASH, AMPK activity is low and mTORC1 is high. In healthy persons, exercise activates AMPK and suppresses mTORC1. We examined the effects of exercise on hepatic ribosomal protein S6 phosphorylation, a downstream target of AMPK and mTORC1 in patients with NASH.
Three subjects with biopsy-proven NASH underwent a structured, 20-week aerobic exercise intervention, five-days a week for 30-min at a moderate intensity (40-55% of VO2max). Immunofluorescence staining for rpS6 phosphorylation in hepatic tissue was quantified by ImageJ software.
Following 20-weeks of aerobic exercise, rpS6 levels were significantly attenuated (3.9 ± 1.9 pre-exercise vs. 1.4 +/0.4 post-exercise, p = 0.04).
These findings suggest exercise modulates the AMPK/mTORC1 pathway in patients with NASH and may guide the design of future studies into the mechanism of how exercise improves NASH and possibly reverses fibrosis.
非酒精性脂肪性肝病（NAFLD）是全球范围内导致肝病的主要原因。非酒精性脂肪性肝炎（NASH）是一种更严重的 NAFLD 类型。运动通过逆转脂肪变性改善 NASH，并可能阻止纤维化。然而，这些相互作用的机制尚不清楚。AMP 激活的蛋白激酶（AMPK）是一种受能量应激激活的燃料感应酶。雷帕霉素靶蛋白复合物 1（mTORC1）是一种营养传感器，可调节蛋白质合成。在 NASH 中，AMPK 活性降低，mTORC1 活性升高。在健康人群中，运动激活 AMPK 并抑制 mTORC1。我们研究了运动对 NASH 患者肝核糖体蛋白 S6 磷酸化的影响，该蛋白是 AMPK 和 mTORC1 的下游靶标。
三名经活检证实患有 NASH 的患者接受了一项结构化的 20 周有氧运动干预，每周 5 天，每天 30 分钟，强度适中（40-55%的 VO2max）。使用 ImageJ 软件对肝组织中 rpS6 磷酸化的免疫荧光染色进行定量。
有氧运动 20 周后，rpS6 水平显著降低（运动前 3.9±1.9 vs. 运动后 1.4+/0.4，p=0.04）。
这些发现表明，运动可调节 NASH 患者的 AMPK/mTORC1 通路，并可能指导未来研究运动如何改善 NASH 以及可能逆转纤维化的机制。
