Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease.
Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease.
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DOI：
10.1016/j.plipres.2012.10.004
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发表时间：
2013-01
影响因子：
13.6
通讯作者：
Young JD
中科院分区：
文献类型：
--
作者：
Leamy AK;Egnatchik RA;Young JD
西方肥胖率的稳步上升与包括非酒精性脂肪肝（NAFLD）在内的众多伴随健康问题的显着增加密切相关。NAFLD的严重程度从简单的脂肪变性到急性脂肪性肝炎不等，但控制这种疾病进展的分子机制知之甚少。最近的文献表明，升高的游离脂肪酸（FFA），特别是饱和的FFA，可能在实验模型和NAFLD患者的脂毒性机制中发挥重要作用。这篇综述强调了重要的细胞途径参与肝脂毒性和肝内脂质饱和度如何控制细胞的命运，在一个升高的FFA负荷。与脂质诱导的细胞凋亡（称为脂凋亡）有因果关系的相关细胞过程包括内质网（ER）应激、氧化应激、线粒体功能障碍和Jun N-末端激酶（JNK）信号传导。相比之下，增加的甘油三酯合成已被证明对脂毒性具有保护作用，尽管是NAFLD的标志性特征之一。对NAFLD进展背后的分子机制进行更细致的了解将为这种日益流行的疾病提供更有针对性和更有效的治疗方法，迄今为止还没有经过证实的药物治疗来预防或逆转其病程。
The steady rise in Western obesity rates has been closely linked to significant increases in a multitude of accompanying health problems including Non-Alcoholic Fatty Liver Disease (NAFLD). NAFLD severity ranges from simple steatosis to acute steatohepatitis, but the molecular mechanisms controlling progression of this disease are poorly understood. Recent literature suggests that elevated free fatty acids (FFAs), especially saturated FFAs, may play an important role in lipotoxic mechanisms, both in experimental models and in NAFLD patients. This review highlights important cellular pathways involved in hepatic lipotoxicity and how the degree of intrahepatic lipid saturation controls cell fate in response to an elevated FFA load. Relevant cellular processes that have been causally linked to lipid-induced apoptosis, known as lipoapoptosis, include endoplasmic reticulum (ER) stress, oxidative stress, mitochondrial dysfunction, and Jun N-terminal kinase (JNK) signaling. In contrast, increased triglyceride synthesis has been shown to have a protective effect against lipotoxicity, despite being one of the hallmark traits of NAFLD. Developing a more nuanced understanding of the molecular mechanisms underlying NAFLD progression will lead to more targeted and effective therapeutics for this increasingly prevalent disease, which to date has no proven pharmacologic treatment to prevent or reverse its course.
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DOI：
10.1152/ajpendo.00272.2005
发表时间：
2006-07-01
影响因子：
5.1
作者：
Collier, Cheryl A.;Bruce, Clinton R.;Dyck, David J.
通讯作者：
Dyck, David J.
影响因子：
4
作者：
Diakogiannaki, Eleftheria;Welters, Hannah J.;Morgan, Noel G.
通讯作者：
Morgan, Noel G.
DOI：
10.1152/ajpregu.00287.2005
发表时间：
2006-01-01
影响因子：
2.8
作者：
Abbasi, F;Chang, SA;Reaven, PD
通讯作者：
Reaven, PD
影响因子：
13.5
作者：
Garcia-Ruiz, Inmaculada;Rodriguez-Juan, Cristina;Solis-Herruzo, Jose A.
通讯作者：
Solis-Herruzo, Jose A.
影响因子：
7.7
作者：
Cnop, M;Hannaert, JC;Pipeleers, DG
通讯作者：
Pipeleers, DG