Dysfunctional Very-Low-Density Lipoprotein Synthesis and Release Is a Key Factor in Nonalcoholic Steatohepatitis Pathogenesis
Dysfunctional Very-Low-Density Lipoprotein Synthesis and Release Is a Key Factor in Nonalcoholic Steatohepatitis Pathogenesis
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DOI：
10.1002/hep.23094
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发表时间：
2009-09-01
期刊：
影响因子：
13.5
通讯作者：
Nakajima, Atsushi
中科院分区：
文献类型：
--
作者：
Fujita, Koji;Nozaki, Yuichi;Nakajima, Atsushi
非酒精性脂肪肝（NAFL）和非酒精性脂肪性肝炎（NASH）的发病机制尚不清楚。在本研究中，我们调查了NAFL和NASH在肝脏脂质代谢产物和血清脂蛋白方面的差异。总共评价了104例经组织学证实的NAFL疾病（NAFLD）（51例NAFL，53例NASH）日本受试者（50例男性和54例绝经后女性）;所有诊断均基于肝活检结果和拟定的诊断标准。为了研究人类NAFL和NASH之间的差异，我们仔细检查了（1）肝脏中的脂质流入，（2）肝脏中的脂质流出，（3）肝脏中的极低密度脂蛋白（VLDL）合成，（4）肝脏中的甘油三酯（TG）代谢物，以及（5）脂质变化和氧化DNA损伤。在NAFL和NASH组中，大多数肝脏脂质代谢产物谱相似。然而，在NASH组中，VLDL合成和肝脏脂质流出受损，并且由于脂质氧化和氧化DNA损伤可能产生了多余的TG。结论：越来越多的文献表明，由VLDL合成障碍引起的肝脏脂肪酸氧化和VLDL分泌的恶化可能会诱导严重的脂质氧化和DNA氧化损伤，影响肝损伤的程度，从而促进NASH的进展。因此，功能失调的VLDL合成和释放可能是进展为NASH的关键因素。（《肝脏病学》2009年;50：772-780。）
The specific mechanisms of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) pathogenesis remain unknown. In the present study we investigated the differences between NAFL and NASH in terms of liver lipid metabolites and serum lipoprotein. In all, 104 Japanese subjects (50 men and 54 postmenopausal women) with histologically verified NAFL disease (NAFLD) (51 with NAFL, 53 with NASH) were evaluated; all diagnoses were based on liver biopsy findings and the proposed diagnostic criteria. To investigate the differences between NAFL and NASH in humans, we carefully examined (1) lipid inflow in the liver, (2) lipid outflow from the liver, (3) very-low-density lipoprotein (VLDL) synthesis in the liver, (4) triglyceride (TG) metabolites in the liver, and (5) lipid changes and oxidative DNA damage. Most of the hepatic lipid metabolite profiles were similar in the NAFL and NASH groups. However, VLDL synthesis and lipid outflow from the liver were impaired, and surplus TGs might have been produced as a result of lipid oxidation and oxidative DNA damage in the NASH group. Conclusion: A growing body of literature suggests that a deterioration in fatty acid oxidation and VLDL secretion from the liver, caused by the impediment of VLDL synthesis, might induce serious lipid oxidation and DNA oxidative damage, impacting the degree of liver injury and thereby contributing to the progression of NASH. Therefore, dysfunctional VLDL synthesis and release may be a key factor in progression to NASH. (HEPATOLOGY 2009;50:772-780.)