Pleiotropic effects of apolipoprotein A-Ⅱ on high-density lipoprotein functionality, adipose tissue metabolic activity and plasma glucose homeostasis

• 来源期刊: 生物医学研究杂志（英文版）
• 学科: 医学
• 年，卷（期）: 2020,（1）
• 页码范围: 14-26
• 页数: 13页
• 分类号: R363
• 语种: 英文

摘要

Apolipoprotein A-Ⅱ (APOA-Ⅱ) is the second most abundant apolipoprotein of high-density lipoprotein (HDL)synthesized mainly by the liver and to a much lesser extent by the intestine.Transgenic mice overexpressing human APOA-Ⅱ present abnormal lipoprotein composition and are prone to atherosclerosis,though in humans the role for APOA-Ⅱ in coronary heart disease remains controversial.Here,we investigated the effects of overexpressed APOA-Ⅱ on HDL structure and function,adipose tissue metabolic activity,glucose tolerance and insulin sensitivity.C57BL/6 mice were infected with an adenovirus expressing human APOA-Ⅱ or a control adenovirus AdGFP,and five days post-infection blood and tissue samples were isolated.APOA-Ⅱ expression resulted in distinct changes in HDL apoproteome that correlated with increased antioxidant and anti-inflammatory activities.No effects on cholesterol efflux from RAW 264.7 macrophages were observed.Molecular analyses in white adipose tissue (WAT) indicated a stimulation of oxidative phosphorylation coupled with respiration for ATP production in mice overexpressing APOA-Ⅱ.Finally,overexpressed APOA-Ⅱ improved glucose tolerance of mice but had no effect on the response to exogenously administered insulin.In summary,expression of APOAⅡ in C57BL/6 mice results in pleiotropic effects with respect to HDL functionality,adipose tissue metabolism and glucose utilization,many of which are beneficial to health.