Involvement of Angpt14 in the pathological mechanisms of steatosis and steatohepatitis

Angpt14参与脂肪变性和脂肪性肝炎的病理机制

• 批准号: 18590746
• 负责人: TOMITA Kengo
• 金额: $ 2.43万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590746/
• 关键词: steatohepatitis; Angiopoietin like protein; 脂肪肝

Nonalcoholic fatty liver disease can be characterized as a hepatic manifestation of a metabolic syndrome. Nonalcoholic steatohepatitis (NASH) is a severe form of this disease. Angptl4, a member of the angiopoietin-like protein family, is primarily secreted by the liver and adipose tissue. It directly inhibits lipoprotein lipase (LPL) activity and elevates serum triglyceride (TG) level. It has also been reported to improve insulin resistance. Since it is secreted by the liver and involved in the regulation of lipid metabolism and insulin resistance, Angptl4 is a potential therapeutic target for metabolic syndrome. It has also been suggested to be closely associated with the pathology of NASH, for which metabolic syndrome is a background factor. Therefore, Angptl4 is also a potential target for new therapeutic strategies for NASH. In the present study, we established a mouse model of NASH using a methionine-choline deficient (MCD) diet, and examined Angptl4 expression in the liver of these mice. The level of hepatic expression of Angptl4 mRNA was significantly lower in groups of mice that were placed on the MCD diet for three or eight weeks than in the control group, suggesting the possibility that decreased Angptl4 expression in the liver is part of the pathological mechanism of NASH. We also separated parenchymal and nonparenchymal cells and examined the expression of Angptl4 mRNA in each fraction. Angptl4 mRNA was largely expressed in hepatocytes. Further study is necessary to determine the importance of this result for the pathological mechanism of NASH.

非酒精性脂肪肝病可以被描述为代谢综合征的肝表现。非酒精性脂肪性肝炎（NASH）是这种疾病的严重形式。 Angptl4是血管生成素样蛋白家族的成员，主要由肝脏和脂肪组织分泌。它直接抑制脂蛋白脂肪酶（LPL）活性，并提高血清甘油三酸酯（TG）水平。据报道，它可以提高胰岛素抵抗。由于它被肝脏分泌，并参与了脂质代谢和胰岛素抵抗的调节，因此ANGPTL4是代谢综合征的潜在治疗靶标。还建议它与纳什的病理密切相关，纳什的病理是代谢综合征是背景因素。因此，ANGPTL4也是NASH新治疗策略的潜在目标。在本研究中，我们使用蛋氨酸 - 胆碱缺乏（MCD）饮食建立了NASH的小鼠模型，并检查了这些小鼠肝脏中的ANGPTL4表达。在MCD饮食上放置三到八个星期的小鼠组ANGPTL4 mRNA的肝表达水平明显低于对照组，这表明肝脏中ANGPTL4表达降低的可能性是NASH病理机制的一部分。我们还分离了实质和非实质细胞，并检查了每个馏分中Angptl4 mRNA的表达。 Angptl4 mRNA在肝细胞中大部分表达。为了确定该结果对NASH的病理机制的重要性，需要进一步的研究。