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肥胖所致心肌重构及相关线粒体稳态失衡机制研究进展

吴庆, 薛润青, 徐曼, 鲁毅, 于晓江, 刘龙珠, 臧伟进^*

西安交通大学医学部药理学系，西安 710061

摘要

肥胖是心血管疾病的重要危险因素，可导致心肌重构等多种心血管疾病。肥胖可影响血流动力学、破坏自主神经平衡、诱导脂肪组织功能障碍和线粒体稳态失衡，从而损伤心肌功能。代谢稳态所需的关键生物化学反应主要发生在线粒体中，线粒体稳态是决定细胞活力的关键因素之一。线粒体稳态的平衡由线粒体分裂和融合、线粒体嵴重构、线粒体生物合成、线粒体自噬、线粒体氧化应激等动态过程调节。线粒体分裂和融合以及线粒体嵴形态不断变化以维持线粒体结构的完整性，且线粒体通过生物合成和自噬降解以维持“健康”的线粒体状态，而活性氧簇可作为信号分子调控细胞内信号转导。肥胖时的脂质过度沉积及脂质合成与分解不平衡诱发线粒体结构和功能的稳态失衡，激活细胞凋亡级联反应并导致心肌重塑。本文就肥胖所致心肌重构的可能机制以及线粒体稳态失衡在其中的重要作用作一简要综述，以期为临床上肥胖所致心血管疾病的防治提供重要策略和潜在靶点。

关键词： 肥胖; 心肌重构; 线粒体稳态

分类号：R3

Recent progress on obesity-induced myocardial remodeling and its possible mechanism of mitochondrial dyshomeostasis

WU Qing, XUE Run-Qing, XU Man, LU Yi, YU Xiao-Jiang, LIU Long-Zhu, ZANG Wei-Jin^*

Department of Pharmacology, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China

Abstract

Obesity is an important risk factor for cardiovascular diseases, which can lead to a variety of cardiovascular diseases including myocardial remodeling. Obesity may induce myocardial dysfunction by affecting hemodynamics, inducing autonomic imbalance, adipose tissue dysfunction, and mitochondrial dyshomeostasis. The key necessary biochemical functions for metabolic homeostasis are performed in mitochondria, and mitochondrial homeostasis is considered as one of the key determinants for cell viability. Mitochondrial homeostasis is regulated by dynamic regulation of mitochondrial fission and fusion, as well as mitochondrial cristae remodeling, biogenesis, autophagy, and oxidative stress. The mitochondrial fission-fusion and morphological changes of mitochondrial cristae maintain the integrity of the mitochondrial structure. The mitochondria maintain a “healthy” state by balancing biogenesis and autophagy, while reactive oxygen species can act as signaling molecules to regulate intracellular signaling. The excessive accumulation of lipids and lipid metabolism disorder in obesity leads to mitochondrial dyshomeostasis, which activate the apoptotic cascade and lead to myocardial remodeling. In this review, we provide an overview of the recent research progress on obesity-induced myocardial remodeling and its possible mechanism of mitochondrial dyshomeostasis.

Key words: obesity; myocardial remodeling; mitochondrial homeostasis

收稿日期：2018-06-25　　录用日期：2018-11-30

通讯作者：臧伟进　　E-mail: zwj@xjtu.edu.cn

DOI: 10.13294/j.aps.2019.0012

引用本文：

吴庆, 薛润青, 徐曼, 鲁毅, 于晓江, 刘龙珠, 臧伟进. 肥胖所致心肌重构及相关线粒体稳态失衡机制研究进展[J]. 生理学报 2019; 71 (2): 216-224.

WU Qing, XUE Run-Qing, XU Man, LU Yi, YU Xiao-Jiang, LIU Long-Zhu, ZANG Wei-Jin. Recent progress on obesity-induced myocardial remodeling and its possible mechanism of mitochondrial dyshomeostasis. Acta Physiol Sin 2019; 71 (2): 216-224 (in Chinese with English abstract).