Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD.
Compromised hepatic mitochondrial fatty acid oxidation and reduced markers of mitochondrial turnover in human NAFLD.
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DOI：
10.1002/hep.32324
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发表时间：
2022-11
期刊：
影响因子：
13.5
通讯作者：
Rector, R. Scott
中科院分区：
文献类型：
--
作者：
Moore, Mary P.;Cunningham, Rory P.;Meers, Grace M.;Johnson, Sarah A.;Wheeler, Andrew A.;Ganga, Rama R.;Spencer, Nicole M.;Pitt, James B.;Diaz-Arias, Alberto;Swi, Ahmed I. A.;Hammoud, Ghassan M.;Ibdah, Jamal A.;Parks, Elizabeth J.;Rector, R. Scott
非酒精性脂肪性肝病（NAFLD）及其更晚期形式的脂肪性肝炎（NASH）与肥胖相关，是心血管、肝脏相关和全因死亡的独立风险因素。在NAFLD和NASH中检查肝线粒体脂肪酸氧化和肝线粒体周转的可用人类数据很少。为了研究这种关系，从接受减肥手术的肥胖患者中获得肝活检组织，并基于肝组织病理学分类将数据聚类为四组：对照组（无疾病）、NAFL（仅脂肪变性）、边界-NASH（脂肪变性伴小叶炎症或肝细胞气球样变）和脂肪变性-NASH（脂肪变性、小叶炎症和肝细胞气球样变）。与对照组相比，D-NASH使肝线粒体完全脂肪酸氧化为CO2和β氧化中的限速酶（β-羟酰辅酶A脱氢酶活性）降低约40-50%。这与肝脏线粒体活性氧产生增加以及NAFL和NASH中线粒体生物发生、自噬、线粒体自噬、分裂和融合的标志物显著减少相对应。这些发现表明，受损的肝脂肪酸氧化和线粒体周转与肥胖患者NAFLD严重程度的增加密切相关。
Nonalcoholic fatty liver disease (NAFLD) and its more advanced form steatohepatitis (NASH) is associated with obesity and is an independent risk factor for cardiovascular, liver-related, and all-cause mortality. Available human data examining hepatic mitochondrial fatty acid oxidation and hepatic mitochondrial turnover in NAFLD and NASH are scant. To investigate this relationship, liver biopsies were obtained from patients with obesity undergoing bariatric surgery and data clustered into four groups based on hepatic histopathological classification: Control (no disease), NAFL (steatosis only), Borderline-NASH (steatosis with lobular inflammation or hepatocellular ballooning), and Definite-NASH (steatosis, lobular inflammation, and hepatocellular ballooning). Hepatic mitochondrial complete fatty acid oxidation to CO2 and the rate limiting enzyme in β-oxidation (β-hydroxyacyl-CoA dehydrogenase activity) were reduced by ~40-50% with D-NASH compared with Control. This corresponded with increased hepatic mitochondrial reactive oxygen species production, as well as dramatic reductions in markers of mitochondrial biogenesis, autophagy, mitophagy, fission and fusion in NAFL and NASH. These findings suggest that compromised hepatic fatty acid oxidation and mitochondrial turnover are intimately linked to increasing NAFLD severity in patients with obesity.
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影响因子：
4.1
作者：
Fletcher JA;Meers GM;Linden MA;Kearney ML;Morris EM;Thyfault JP;Rector RS
通讯作者：
Rector RS
影响因子：
29.4
作者：
Iozzo, Patricia;Bucci, Marco;Nuutila, Pirjo
通讯作者：
Nuutila, Pirjo
影响因子：
6.7
作者：
Kotronen, Anna;Seppala-Lindroos, Anneli;Yki-Javinen, Hannele
通讯作者：
Yki-Javinen, Hannele
影响因子：
3.3
作者：
Laughlin, M. Harold;Padilla, Jaume;Davis, J. Wade
通讯作者：
Davis, J. Wade
影响因子：
4.8
作者：
Liu, Hui-Yu;Han, Jianmin;Cao, Wenhong
通讯作者：
Cao, Wenhong