Glycosylphosphatidylinositol-specific phospholipase D in nonalcoholic fatty liver disease: A preliminary study
Glycosylphosphatidylinositol-specific phospholipase D in nonalcoholic fatty liver disease: A preliminary study
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DOI：
10.1210/jc.2006-0075
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发表时间：
2006-06-01
影响因子：
5.8
通讯作者：
Deeg, Mark A.
中科院分区：
文献类型：
--
作者：
Chalasani, Naga;Vuppalanchi, Raj;Deeg, Mark A.
背景：最近的研究表明，非酒精性脂肪性肝病(NAFLD)患者的新生脂肪生成增加。NAFLD患者也存在血脂异常。这些血脂异常可能在一定程度上与胰岛素抵抗有关，胰岛素抵抗在NAFLD患者中很常见。胰岛素抵抗与脂代谢相关蛋白的改变有关，包括参与甘油三酯代谢的糖基磷脂酰肌醇特异性磷脂酶D(GPI-PLD)。目的：本研究的目的是确定NAFLD患者血清和肝脏GPI-PLD水平是否发生改变。设计与患者：1)非糖尿病非酒精性脂肪性肝炎患者血清GPI-PLD水平，与对照组比较；2)正常肝脏或NAFLD患者肝脏GPI-PLD基因表达；结果：非酒精性脂肪性肝炎患者血清GPI-PLD水平显著高于正常对照组(119mU/-24vs105+/-15mU g/ml，P=0.047)。非酒精性脂肪肝患者肝组织中GPI-PLD基因的表达水平是正常肝患者的近3倍(3.1+/-2.6vs.1.1+/-1.0个单位/微克总RNA，P=0.026)。结论：NAFLD患者血清和肝脏中GPI-PLD的表达水平升高，其体外高表达与新生脂肪生成基因的表达增加有关。这些结果提示GPI-PLD可能在NAFLD的发病机制和/或代谢特征中起作用，值得进一步研究。
Context: Recent studies demonstrated that de novo lipogenesis is increased in patients with nonalcoholic fatty liver disease (NAFLD). Patients with NAFLD also have plasma lipid abnormalities. These lipid abnormalities may in part be related to insulin resistance, which is common in patients with NAFLD. Insulin resistance is associated with alterations in proteins involved in lipid metabolism including glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), which is involved in triglyceride metabolism.Objective: The objective of the study was to determine whether alterations in serum and hepatic levels of GPI-PLD occur in patients with NAFLD.Design and Patients: We examined the following: 1) levels of serum GPI-PLD in nondiabetics with nonalcoholic steatohepatitis, compared with matched controls; 2) hepatic expression of GPI-PLD mRNA in patients with normal liver or NAFLD; and 3) effect of overexpressing GPI-PLD vs. beta-galactosidase (control) on global gene expression in a human hepatoma cell line.Results: The serum levels of GPI-PLD were significantly higher in patients with nonalcoholic steatohepatitis than in matched controls (119 +/- 24 vs. 105 +/- 15 mu g/ml, P = 0.047). The hepatic expression of GPI-PLD mRNA was increased nearly 3-fold in NAFLD patients, compared with patients with normal liver (3.1 +/- 2.6 vs. 1.1 +/- 1.0 arbitrary units per microgram total RNA, P = 0.026). Finally, overexpressing GPI-PLD was associated with an increase in de novo lipogenesis genes.Conclusions: Patients with NAFLD have elevated serum levels and hepatic expression of GPI-PLD, and its overexpression in vitro is associated with increased expression of de novo lipogenesis genes. These results suggest that GPI-PLD may play a role in the pathogenesis of NAFLD and/or its metabolic features and warrants further investigation.