Role of alpha-syntrophin in non-alcoholic fatty liver disease

α-肌营养蛋白在非酒精性脂肪肝中的作用

• 批准号: 299715236
• 负责人: Professorin Dr. Christa Büchler
• 金额: --
• 依托单位: Klinik und Poliklinik für Innere Medizin I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/299715236?language=en
• 关键词: Role; alpha; syntrophin; non; alcoholic

Alpha-Syntrophin (SNTA) is an adaptor protein whose function in the liver has not been clarified yet. Our group has shown that SNTA deficient mice are protected from insulin resistance, liver steatosis and hepatic inflammation when fed a high fat diet. Fatty liver is a risk factor to develop progressive liver disease. SNTA is induced in murine NASH. Whether SNTA deficiency ameliorates steatosis, inflammation and fibrosis in animal models of non-alcoholic steatohepatitis will be analyzed in the current application. This study includes analysis of lipid species by mass spectrometry. The composition and inflammatory response of hepatic immune cells in the NASH models will be characterized. The role of SNTA in hepatocyte lipid storage and activation of hepatic stellate cells will be studied. The effect of lipopolysaccharide and muramyldipeptide in macrophages will be further analyzed in-vitro. The expression of newly identified SNTA regulated / associated proteins and of well-described SNTA binding proteins will be analyzed in SNTA-/- mice liver and in murine non-alcoholic fatty liver disease (NAFLD). NAFLD is the most prevalent cause of chronic liver disease and data from our group suggest a role of SNTA in insulin resistance and NAFLD. The current project intends to further corroborate these findings.

α-促链蛋白（SNTA）是一种衔接蛋白，尚未阐明其在肝脏中的功能。我们的小组表明，SNTA不足的小鼠免受胰岛素抵抗，肝脏脂肪变性和肝炎症的抗药性。脂肪肝是发展进行性肝病的危险因素。 SNTA在鼠纳什诱发。 SNTA缺乏能够改善非酒精性脂肪性肝炎动物模型中的脂肪变性，炎症和纤维化是否会在当前应用中分析。这项研究包括通过质谱法分析脂质物种。 NASH模型中肝免疫细胞的组成和炎症反应将被表征。将研究SNTA在肝细胞脂质储存中的作用和肝星状细胞的激活。脂多糖和穆拉米二肽在巨噬细胞中的影响将进一步分析。新鉴定的SNTA调节 /相关蛋白的表达和描述良好的SNTA结合蛋白的表达将在SNTA - / - 小鼠肝脏和鼠非酒精性脂肪肝病（NAFLD）中进行分析。 NAFLD是慢性肝病的最普遍原因，我们组的数据表明SNTA在胰岛素抵抗和NAFLD中的作用。当前的项目旨在进一步证实这些发现。

项目成果

The adaptor protein alpha-syntrophin is reduced in human non-alcoholic steatohepatitis but is unchanged in hepatocellular carcinoma.

• DOI: 10.1016/j.yexmp.2017.09.005
• 发表时间: 2017-10
• 期刊: Experimental and molecular pathology
• 影响因子: 3.6
• 作者: L. Rein‐Fischboeck;R. Pohl;E. Haberl;T. Weiss;C. Buechler

Tubulin alpha 8 is expressed in hepatic stellate cells and is induced in transformed hepatocytes

微管蛋白 α 8 在肝星状细胞中表达，并在转化的肝细胞中被诱导

• DOI: 10.1007/s11010-016-2926-4
• 发表时间: 2017
• 期刊: Molecular and Cellular Biochemistry
• 影响因子: 4.3
• 作者: Rein-Fischboeck L;Pohl R;Haberl EM;Zimny S;Neumann M;Eisinger K;Weiss TS;Krautbauer S;Buechler C
• 通讯作者: Buechler C

Alpha-syntrophin deficient mice are protected from adipocyte hypertrophy and ectopic triglyceride deposition in obesity.

α-肌营养不良蛋白缺陷小鼠免受脂肪细胞肥大和肥胖症异位甘油三酯沉积的影响

• DOI: 10.1016/j.yexmp.2018.04.003
• 发表时间: 2018
• 期刊: Experimental and molecular pathology
• 影响因子: 3.6
• 作者: Eisinger K;Rein-Fischboeck L;Neumeier M;Schmidhofer S;Pohl R;Haberl EM;Liebisch G;Kopp A;Schmid A;Krautbauer S;Buechler C
• 通讯作者: Buechler C

Alpha-syntrophin dependent expression of tubulin alpha 8 protein in hepatocytes

肝细胞中微管蛋白α8蛋白的α-肌营养蛋白依赖性表达

• DOI: 10.1007/s13105-018-0645-x
• 发表时间: 2018
• 期刊: Journal of Physiology and Biochemistry
• 影响因子: 3.4
• 作者: Rein- Fischboeck L;Bajraktari G;Pohl R;Feder S;Eisinger K;Mages W;Haberl EM;Buechler C
• 通讯作者: Buechler C

Alpha-syntrophin null mice are protected from non-alcoholic steatohepatitis in the methionine-choline-deficient diet model but not the atherogenic diet model.

• DOI: 10.1016/j.bbalip.2018.02.006
• 发表时间: 2018-05
• 期刊: Biochimica et biophysica acta. Molecular and cell biology of lipids
• 作者: L. Rein‐Fischboeck;E. Haberl;R. Pohl;V. Schmid;S. Feder;S. Krautbauer;G. Liebisch;C. Buechler