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Exercise Attenuates Ribosomal Protein Six Phosphorylation in Fatty Liver Disease.

运动减少脂肪肝中核糖体蛋白六磷酸化。

  • 影响因子:2.46
  • DOI:10.1007/s10620-020-06226-1
  • 作者列表:"Stine JG","Xu D","Schmitz K","Sciamanna C","Kimball SR
  • 发表时间:2020-04-01
Abstract

INTRODUCTION: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. METHODS: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. RESULTS: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). CONCLUSIONS: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.

摘要

导读: 非酒精性脂肪性肝病 (NAFLD) 是全球肝病的首要病因。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,这些相互作用的潜在机制尚不清楚。AMP 激活的蛋白激酶 (AMPK) 是一种被能量应激激活的燃料敏感酶。哺乳动物雷帕霉素复合物靶点 1 (mTORC1) 是一种调节蛋白质合成的营养传感器。在 NASH 中,AMPK 活性低,mTORC1 高。在健康人中,运动激活 AMPK 并抑制 mtorc1。我们检测了运动对 NASH 患者 AMPK 和 mTORC1 下游靶点肝核糖体蛋白 S6 磷酸化的影响。 方法: 3 例经活检证实的 NASH 受试者接受了为期 20 周的结构化有氧运动干预,每周 5 天,30 分钟,中等强度 (VO2max 的 40-55%)。用 ImageJ 软件定量肝组织中 rpS6 磷酸化的免疫荧光染色。 结果: 20 周有氧运动后,rpS6 水平显著减弱 (运动前 3.9 ± 1.9 vs 运动后 1.4 ± 0.4,p = 0.04)。 结论: 这些发现表明运动调节 NASH 患者的 AMPK/mTORC1 通路,并可能指导未来研究的设计,了解运动如何改善 NASH 并可能逆转纤维化的机制。

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影响因子:3.87
发表时间:2020-02-01
DOI:10.1111/liv.14321
作者列表:["Chen VL","Chen Y","Du X","Handelman SK","Speliotes EK"]

METHODS:BACKGROUND AND AIMS:Cirrhosis is characterized by extensive fibrosis of the liver and is a major cause of liver-related mortality. Cirrhosis is partially heritable but genetic contributions to cirrhosis have not been systemically explored. Here, we carry out association analyses with cirrhosis in two large biobanks and determine the effects of cirrhosis associated variants on multiple human disease/traits. METHODS:We carried out a genome-wide association analysis of cirrhosis as a diagnosis in UK BioBank (UKBB; 1088 cases vs. 407 873 controls) and then tested top-associating loci for replication with cirrhosis in a hospital-based cohort from the Michigan Genomics Initiative (MGI; 875 cases of cirrhosis vs. 30 346 controls). For replicating variants or variants previously associated with cirrhosis that also affected cirrhosis in UKBB or MGI, we determined single nucleotide polymorphism effects on all other diagnoses in UKBB (PheWAS), common metabolic traits/diseases and serum/plasma metabolites. RESULTS:Unbiased genome-wide association study identified variants in/near PNPLA3 and HFE, and candidate variant analysis identified variants in/near TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4 and IFNL4 that reproducibly affected cirrhosis. Most affected liver enzyme concentrations and/or aspartate transaminase-to-platelet ratio index. PheWAS, metabolic trait and serum/plasma metabolite association analyses revealed effects of these variants on lipid, inflammatory and other processes including new effects on many human diseases and traits. CONCLUSIONS:We identified eight loci that reproducibly associate with population-based cirrhosis and define their diverse effects on human diseases and traits.

翻译标题与摘要 下载文献
影响因子:2.57
发表时间:2020-02-01
DOI:10.1111/eci.13198
作者列表:["Li H","Wieser A","Zhang J","Liss I","Markwardt D","Hornung R","Neumann-Cip AC","Mayerle J","Gerbes A","Steib CJ"]

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