Intracellular C3 prevents hepatic steatosis by promoting autophagy and very-low-density lipoprotein secretion
Intracellular C3 prevents hepatic steatosis by promoting autophagy and very-low-density lipoprotein secretion
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细胞内C3通过促进自噬和极低密度脂蛋白分泌来预防肝脏脂肪变性
DOI：
10.1096/fj.202100856r
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Hong Zhou
中科院分区：
文献类型：
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作者：
Yinling Li;Yeqin Sha;Haitao Wang;Lianping He;Longjun Li;Shuang Wen;Liang Shen;Weiguo Hu;Hong Zhou
补体C3主要由肝细胞合成，作为激活补体级联反应的三种不同途径的收敛点。在肝细胞中以极高的浓度存在，对其研究的ePatitic功能知之甚少。从机械上讲，由于C3和自噬相关的16（如1），C3缺乏受损的肝细胞中的脂肪症受损，这对于自溶剂体组装而言至关重要。Furthermore。随后影响蛋白质二硫化物的表达。异构酶和微粒体TG转移蛋白的活性，最终会损害肝炎的产生非常低密度的脂蛋白（VLDLS）。 - 我们的研究表明，C3促进了脂肪症，以促进肝细胞中的VLDL分泌，从而在平衡肝脏中的TG水平中起着重要作用。
Complement component C3, mainly synthesized by hepatocytes, acts as the convergence point of three different pathways in activating the complement cascade. Besides its well-established roles in the extracellular milieu, C3 performs various intracellular functions such as immunomodulation and pathogen recognition..Although C3 is present at extremely high concentrations in hepatocytes, little is known about its intrahepatic function. In this study, we found that C3 knockout (C3−/−) mice displayed accelerated hepatic triglyceride (TG) accumulation compared with C57BL/6J wild type mice. Mechanistically, C3 deficiency impaired lipophagy in hepatocytes, owing to the disrupted interaction between C3 and autophagy-related 16 like 1, which is essential for autolysosome assembly..Furthermore, lipophagy deficiency affected the function of the endoplasmic reticulum in C3−/− mice, subsequently affecting the expression of protein disulfide.isomerase and activity of microsomal TG transfer protein, and ultimately impairing the production of hepatic very-low-density lipoproteins (VLDLs). Rapamycin.and thapsigargin treatment accelerated VLDL secretion and alleviated hepatic lipid accumulation in C3−/− mice. Our study demonstrates that C3 promotes lipophagy to facilitate VLDL secretion in hepatocytes, thus playing an essential role in balancing TG levels in the liver.