Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease.
Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease.
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DOI：
10.1007/s00018-018-2860-6
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发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Tveden-Nyborg P
中科院分区：
文献类型：
--
作者：
Ipsen DH;Lykkesfeldt J;Tveden-Nyborg P
非酒精性脂肪性肝病(NAFLD)是目前世界上最常见的肝病，估计影响多达四分之一的人口。以肝脏脂肪变性为特征的NAFLD与多种有害影响和死亡率增加有关。该叙述性综述探讨了NAFLD患者肝脏脂肪变性的分子机制，重点介绍了促进肝脏脂肪代谢平衡的四条主要途径。肝脏脂肪变性是脂肪摄取超过脂肪处置的结果，即摄取脂肪酸和从头脂肪生成超过脂肪酸氧化和输出。在NAFLD中，肝脏摄取和新生脂肪生成增加，而脂肪酸氧化的代偿性增强不足以使血脂水平正常化，甚至可能通过诱导氧化应激而促进细胞损伤和疾病进展，尤其是线粒体功能受损以及过氧化体和细胞色素氧化增加。虽然脂肪出口最初增加，但它停滞不前，甚至可能随着疾病的进展而减少，维持脂质的积累。在脂肪细胞凋亡的推动下，肝脏脂肪变性导致全身代谢紊乱，对多个器官产生不利影响，使与NAFLD相关的脂代谢异常与当前许多与生活方式相关的疾病密切相关。
Non-alcoholic fatty liver disease (NAFLD) is currently the world’s most common liver disease, estimated to affect up to one-fourth of the population. Hallmarked by hepatic steatosis, NAFLD is associated with a multitude of detrimental effects and increased mortality. This narrative review investigates the molecular mechanisms of hepatic steatosis in NAFLD, focusing on the four major pathways contributing to lipid homeostasis in the liver. Hepatic steatosis is a consequence of lipid acquisition exceeding lipid disposal, i.e., the uptake of fatty acids and de novo lipogenesis surpassing fatty acid oxidation and export. In NAFLD, hepatic uptake and de novo lipogenesis are increased, while a compensatory enhancement of fatty acid oxidation is insufficient in normalizing lipid levels and may even promote cellular damage and disease progression by inducing oxidative stress, especially with compromised mitochondrial function and increased oxidation in peroxisomes and cytochromes. While lipid export initially increases, it plateaus and may even decrease with disease progression, sustaining the accumulation of lipids. Fueled by lipo-apoptosis, hepatic steatosis leads to systemic metabolic disarray that adversely affects multiple organs, placing abnormal lipid metabolism associated with NAFLD in close relation to many of the current life-style-related diseases.
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影响因子：
5.6
作者：
Auguet T;Berlanga A;Guiu-Jurado E;Martinez S;Porras JA;Aragonès G;Sabench F;Hernandez M;Aguilar C;Sirvent JJ;Del Castillo D;Richart C
通讯作者：
Richart C
影响因子：
5.1
作者：
Brunt, Elizabeth M.
通讯作者：
Brunt, Elizabeth M.
DOI：
10.1097/meg.0b013e328345c8c7
发表时间：
2011-05
影响因子：
2.1
作者：
Dasarathy S;Yang Y;McCullough AJ;Marczewski S;Bennett C;Kalhan SC
通讯作者：
Kalhan SC
影响因子：
2.2
作者：
Auinger, A.;Valenti, L.;Rubin, D.
通讯作者：
Rubin, D.
影响因子：
4.8
作者：
Améen, C;Edvardsson, U;Oscarsson, J
通讯作者：
Oscarsson, J