Abstract
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 APOA-Ⅱ 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.
Highlights
Apolipoprotein A-II (APOA-II) is the second most abundant apolipoprotein of high-density lipoprotein (HDL)[1], composed of 77 amino acids and synthesized mainly by the liver and to a much lesser extent by the intestine
We investigated the effects of increased APOA-II expression on HDL structure and function, adipose tissue metabolic activity, glucose tolerance and insulin sensitivity using adenovirus-mediated gene transfer of human APOAII to C57BL/6 mice
APOA-II expression increased the levels of APOCs (APOC-I, APOC-II and APOC-III) though in different lipoprotein fractions
Summary
Apolipoprotein A-II (APOA-II) is the second most abundant apolipoprotein of high-density lipoprotein (HDL)[1], composed of 77 amino acids and synthesized mainly by the liver and to a much lesser extent by the intestine. It has been proposed that APOA-II plays a crucial role in HDL particle synthesis, composition and function[2]. Transgenic mice that overexpress human APOA-II had abnormal lipoprotein composition, increased high-density lipoprotein cholesterol (HDL-C) levels and were prone to atherosclerosis[4]. Studies in CLC number: R363, Document code: A The authors reported no conflict of interests.
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