Hepatic metabolic adaptation and adipose tissue expansion are altered in mice with steatohepatitis induced by high-fat high sucrose diet
Hepatic metabolic adaptation and adipose tissue expansion are altered in mice with steatohepatitis induced by high-fat high sucrose diet
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DOI：
10.1016/j.jnutbio.2020.108559
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发表时间：
2021-03-01
影响因子：
5.6
通讯作者：
Joven, Jorge
中科院分区：
文献类型：
--
作者：
Baiges-Gaya, Gerard;Fernandez-Arroyo, Salvador;Joven, Jorge
背景：肥胖是一种慢性进行性疾病，伴有多种代谢改变。非酒精性脂肪性肝病(NAFLD)是肥胖的重要并存疾病，可发展为非酒精性脂肪性肝炎(NASH)、肝硬变或肝癌。本研究旨在阐明高脂高糖饮食诱导的小鼠NAFLD发生过程中肝脏和脂肪组织代谢变化的分子机制。方法：24只雄性C57BL/6J小鼠随机分为3组，每组8只，分别给予高脂饮食(HFD)、高脂饮食(HFD)和高脂高糖饮食(HF-HSD)喂养20周。处死时，取肝脏和脂肪组织进行组织病理学、代谢组学和蛋白质表达分析。结果：HF-HSD(而不是HFD)与NASH和氧化应激增加相关。这些动物表现出对肝脏自噬的抑制和AMP激活的蛋白激酶/哺乳动物雷帕霉素活性靶标的改变。我们还观察到，受损线粒体的增加对代谢适应能力产生了不利影响。NASH的发生与脂肪组织动力学的变化以及内脏脂肪组织中饱和脂肪酸、单不饱和脂肪酸和多不饱和脂肪酸含量的增加有关。结论：HF-HSD导致代谢受阻，肝线粒体转换率降低。此外，脂肪酸的持续积聚导致脂肪组织功能障碍和肝脏脂肪积聚，这有利于NASH的进展。(C)2020 Elsevier Inc.保留所有权利。
Background : Obesity is a chronic progressive disease with several metabolic alterations. Nonalcoholic fatty liver disease (NAFLD) is an important co morbidity of obesity that can progress to nonalcoholic steatohepatitis (NASH), cirrhosis or hepatocarcinoma. This study aimed at clarifying the molecular mechanisms underlying the metabolic alterations in hepatic and adipose tissue during high-fat high-sucrose diet-induced NAFLD development in mice. Methods : Twenty-four male mice (C57BL/6J) were randomly allocated into 3 groups ( n = 8 mice per group) to receive a chow diet, a high-fat diet (HFD), or a high-fat high-sucrose diet (HF-HSD) for 20 weeks. At sacrifice, liver and adipose tissue were obtained for histopathological, metabolomic, and protein expression analyses. Results : HF-HSD (but not HFD) was associated with NASH and increased oxidative stress. These animals presented an inhibition of hepatic autophagy and alterations in AMP-activated protein kinase/mammalian target of rapamycin activity. We also observed that the ability of metabolic adaptation was adversely affected by the increase of damaged mitochondria. NASH development was associated with changes in adipose tissue dynamics and increased amounts of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids in visceral adipose tissue. Conclusion : HF-HSD led to a metabolic blockage and impaired hepatic mitochondria turnover. In addition, the continuous accumulation of fatty acids produced adipose tissue dysfunction and hepatic fat accumulation that favored the progression to NASH. (c) 2020 Elsevier Inc. All rights reserved.