Acetylcholine reduces palmitate-induced cardiomyocyte apoptosis by promoting lipid droplet lipolysis and perilipin 5-mediated lipid droplet-mitochondria interaction
Acetylcholine reduces palmitate-induced cardiomyocyte apoptosis by promoting lipid droplet lipolysis and perilipin 5-mediated lipid droplet-mitochondria interaction
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乙酰胆碱通过促进脂滴脂肪分解和周脂素 5 介导的脂滴-线粒体相互作用来减少棕榈酸盐诱导的心肌细胞凋亡
DOI：
10.1080/15384101.2021.1965734
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发表时间：
2021-08
期刊：
影响因子：
4.3
通讯作者：
Zang Weijin
中科院分区：
文献类型：
--
作者：
Wu Qing;Zhao Ming;He Xi;Xue Runqing;Li Dongling;Yu Xiaojiang;Wang Shengpeng;Zang Weijin
ABSTRACT Lipid droplets (LDs), which are neutral lipid storage organelles, are important for lipid metabolism and energy homeostasis. LD lipolysis and interactions with mitochondria are tightly coupled to cellular metabolism and may be potential targets to buffer the effects of excessive toxic lipid species levels. Acetylcholine (ACh), the major neurotransmitter of the vagus nerve, exhibits cardioprotective effects. However, limited research has focused on its effects on LD lipolysis and the LD-mitochondria association in fatty acid (FA) overload models. Here, we reveal that palmitate (PA) induces an increase in expression of the FA transport protein cluster of differentiation 36 (CD36) and LD formation; remarkably reduces the expression of lipases involved in triacylglycerol (TAG) lipolysis, such as adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL); impairs LD-mitochondria interaction; and decreases perilipin 5 (PLIN5) expression, resulting in LD accumulation and mitochondrial dysfunction, which ultimately lead to cardiomyocyte apoptosis. ACh significantly upregulates PLIN5 expression and improved LD lipolysis and the LD-mitochondria association. Moreover, ACh reduces CD36 expression, LD deposition and mitochondrial dysfunction, ultimately suppressing apoptosis in PA-treated neonatal rat ventricular cardiomyocytes (NRVCs). Knockdown of PLIN5, which plays a role in LD-mitochondria contact site formation, abolishes the protective effects of ACh in PA-treated NRVCs. Thus, ACh protects cardiomyocytes from PA-induced apoptosis, at least partly, by promoting LD lipolysis and activating LD-mitochondria interactions via PLIN5. These findings may aid in developing novel therapeutic approaches that target LD lipolysis and PLIN5-mediated LD-mitochondria interactions to prevent or alleviate lipotoxic cardiomyopathy.
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