Blue California, Rancho Santa Margarita, CA 92688, USA; University of Cincinnati School of Medicine, Cincinnati, OH 45215, USA.
University of Cincinnati School of Medicine, Cincinnati, OH 45215, USA.
Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Sep;1867(9):159185. doi: 10.1016/j.bbalip.2022.159185. Epub 2022 May 26.
The discovery of apolipoprotein A5 (APOA5) in 2001 has raised a number of intriguing questions about its role in lipid transport and triglyceride (TG) homeostasis. Genome-wide association studies have consistently identified APOA5 as a regulator of plasma TG levels, which is further supported by studies in transgenic and knockout mouse models. The present review describes recent concepts pertaining to the roles of APOA5 in TG metabolism as related to the vascular compartment, liver, adipose tissue and the gut. Recent evidence indicates that APOA5 may also affect postprandial TG metabolism through influencing chylomicron formation and transport by the intestine into the intestinal lymph. While substantial evidence supports the notion that APOA5 plays both extracellular and intracellular roles in TG homeostasis, mysteries remain on how this low-abundance, liver-derived protein may modulate TG homeostasis, including via the gut. Given the strong correlation between elevated plasma TG and cardiometabolic diseases, there is great scientific and public interest in understanding the intriguing mysteries presented by APOA5.
载脂蛋白 A5（APOA5）于 2001 年被发现，其在脂质转运和甘油三酯（TG）稳态中的作用引发了诸多有趣的问题。全基因组关联研究一致表明 APOA5 是血浆 TG 水平的调节剂，转基因和基因敲除小鼠模型的研究进一步支持了这一观点。本综述描述了与血管腔、肝脏、脂肪组织和肠道相关的 APOA5 在 TG 代谢中的作用的最新概念。最近的证据表明，APOA5 还可能通过影响肠内乳糜微粒的形成和运输来影响餐后 TG 代谢。尽管大量证据支持 APOA5 在 TG 稳态中发挥细胞外和细胞内作用的观点，但仍不清楚这种低丰度的肝脏来源蛋白如何通过肠道来调节 TG 稳态。鉴于血浆 TG 升高与心血管代谢疾病之间存在很强的相关性，科学界和公众对理解 APOA5 所呈现的这些令人着迷的奥秘有着浓厚的兴趣。
