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载脂蛋白C3在非酒精性脂肪肝、糖脂代谢和胰岛β细胞功能调节中的作用

闫姗^1,2, 丁智勇³, 高媛^2,4, 毛王佳^1,2, 程晓芸^1,3,*

¹同济大学附属第十人民医院内分泌科，上海 200072；²同济大学医学院，上海 200092；³同济大学附属第十人民医院崇明分院内分泌科，上海 202157；⁴广饶县人民医院内分泌科，东营 257300

摘要

作为载脂蛋白C (apolipoprotein C, ApoC)家族中含量较高的一员，ApoC3在甘油三酯代谢的调节中起着主要作用，同时在心血管疾病、糖脂代谢紊乱等疾病的发生、发展中发挥重要作用。非酒精性脂肪肝(nonalcoholic fatty liver disease, NAFLD)是指患者在不存在慢性饮酒史及其他损肝因素的情况下，肝脏内有大量脂肪堆积的现象。既往有大量的研究表明，ApoC3的基因多态性、高表达与NAFLD之间存在相关性，但仍存有争议。本文以高甘油三酯血症(hypertriglyceridemia, HTG)为背景，综述ApoC3与NAFLD、糖脂代谢及胰岛β细胞功能之间的关联，表明ApoC3不仅可以通过抑制脂蛋白脂酶(lipoprotein lipase, LPL)和肝脂酶(hepatic lipase, HL)的活性、延缓甘油三酯在血浆中的分解来维持机体在禁食期间的能量代谢，还可在胰岛素抵抗的情况下显著升高，促使肝脏分泌大量极低密度脂蛋白(very low-density lipoprotein, VLDL)而诱发HTG，因此靶向抑制ApoC3将成为治疗HTG的新策略。但对于NAFLD来说，ApoC3不是一个独立的“贡献者”。同样地，本研究组前期研究显示，ApoC3并不能成为引发ApoC3转基因小鼠β细胞功能障碍的独立因素，但在营养过剩状态下，ApoC3高表达所引发的HTG可能会加剧高血糖和胰岛素抵抗对胰岛β细胞功能的影响，其作用机制有待进一步深入讨论。

关键词： 载脂蛋白C3; 高甘油三酯血症; 非酒精性脂肪肝; 胰岛β细胞功能

The role of apolipoprotein C3 in the regulation of nonalcoholic fatty liver disease,  glucose and lipid metabolism, and islet β cell function

YAN Shan^1,2, DING Zhi-Yong³, GAO Yuan^2,4, MAO Wang-Jia^1,2, CHENG Xiao-Yun^1,3,*

¹Department of Endocrinology and Metabolism, Tenth People’s Hospital of Tongji University, Shanghai 200072, China；²School of Medicine, Tongji University, Shanghai 200092, China；³Department of Endocrinology and Metabolism, Chongming Branch, Tenth People’s Hospital of Tongji University, Shanghai 202157, China；⁴Department of Endocrinology, the People’s Hospital of Guangrao, Dongying 257300, China

Abstract

As a member of the apolipoprotein C (ApoC) family with a relatively high content, ApoC3 plays a major role in the regulation of triglyceride metabolism, and plays an important role in the occurrence and development of cardiovascular diseases, glucose and lipid metabolism disorders. Nonalcoholic fatty liver disease (NAFLD) refers to the accumulation of a large amount of fat in the liver in the absence of a history of chronic alcohol consumption or other damage to the liver. A large number of previous studies have shown that there is a correlation between the gene polymorphism and high expression of ApoC3 and NAFLD. In the context of hypertriglyceridemia (HTG), this article reviews the relationship between ApoC3 and NAFLD, glucose and lipid metabolism, and islet β cell function, showing that ApoC3 can not only inhibit lipoprotein lipase (LPL) and hepatic lipase (HL) activity, delay the decomposition of triglyceride in plasma to maintain the body’s energy metabolism during fasting, but also be significantly increased under insulin resistance, prompting the liver to secrete a large amount of very low-density lipoprotein (VLDL) to induce HTG. Therefore, targeting and inhibiting ApoC3 might become a new approach to treat HTG. Increasing evidence suggests that ApoC3 does not appear to be an independent “contributor” to NAFLD. Similarly, our previous studies have shown that ApoC3 is not an independent factor triggering islet β cell dysfunction in ApoC3 transgenic mice, but in a state of excess nutrition, HTG triggered by ApoC3 high expression may exacerbate the effects of hyperglycemia and insulin resistance on islet β cell function, and the underlying mechanism remains to be further discussed.

Key words: apolipoprotein C3; hypertriglyceridemia; nonalcoholic fatty liver disease; islet β cell function

收稿日期：　　录用日期：

通讯作者：程晓芸　　E-mail: chenxiaoyun0210@163.com

DOI: 10.13294/j.aps.2023.0086

引用本文：

闫姗, 丁智勇, 高媛, 毛王佳, 程晓芸. 载脂蛋白C3在非酒精性脂肪肝、糖脂代谢和胰岛β细胞功能调节中的作用[J]. 生理学报 2023; 75 (6): 767-778.

YAN Shan, DING Zhi-Yong, GAO Yuan, MAO Wang-Jia, CHENG Xiao-Yun. The role of apolipoprotein C3 in the regulation of nonalcoholic fatty liver disease,  glucose and lipid metabolism, and islet β cell function. Acta Physiol Sin 2023; 75 (6): 767-778 (in Chinese with English abstract).