Testosterone deficiency accelerates early stage atherosclerosis in miniature pigs fed a high-fat and high-cholesterol di
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Testosterone deficiency accelerates early stage atherosclerosis in miniature pigs fed a high‑fat and high‑cholesterol diet: urine 1H NMR metabolomics targeted analysis Liqun Deng1,2 · Danting Fu1,3 · Liang Zhu1,2 · Junjie Huang1,2 · Yun Ling1,2 · Zhaowei Cai1,2 Received: 30 July 2020 / Accepted: 16 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract To gain insights into the role of testosterone in the development of atherosclerosis and its related metabolic pathways, we applied a proton nuclear magnetic resonance (1H NMR)-based metabolomics approach to investigate urine metabolic profiles in miniature pigs fed a high-fat and high-cholesterol (HFC) diet among intact male pigs (IM), castrated male pigs (CM) and castrated male pigs with testosterone replacement (CMT). Our results showed that testosterone deficiency significantly increased atherosclerotic lesion areas, intima-media thickness, as well as serum lipid levels in the CM pigs. Moreover, seventeen significantly changed metabolites were identified in both IM vs. CM and CMT vs. CM groups. Among these, seven were shared between the two comparative groups and were all significantly reduced in the urine of the CM group but rescued in the CMT group. In addition, the correlation analysis demonstrated that several metabolites, including niacinamide, myo-inositol, choline and 3-hydroxyisovalerate, were negatively correlated with atherosclerotic lesion areas. Our study demonstrated that testosterone deficiency accelerated early AS formation in HFC diet-fed pigs, which involved several metabolites predominantly related to lipid metabolism, inflammation, oxidative stress and endothelial disorders. Our results reveal potential pathways in the pathogenesis of atherosclerosis caused by testosterone deficiency and HFC diet. Keywords Atherosclerosis · Miniature pigs · 1H-NMR metabolomics · High-fat and high cholesterol diet · Testosterone deficiency
Introduction Atherosclerosis is a complex multifactorial disease and a major underlying pathology for cardiovascular disease, which is the leading cause of death worldwide [1]. Many Liqun Deng and Danting Fu have equal contributions to the work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11010-020-03987-1) contains supplementary material, which is available to authorized users. * Zhaowei Cai [email protected] 1
Laboratory Animal Research Center, Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
2
Institute of Comparative Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
3
Department of Experimental Animals, Zhejiang Academy of Traditional Chinese Medicine, Hangzhou 310012, China
factors, including age, sex, genetics and environment, influence the development of atherosclerosis. Recent epidemiological studies have shown that the reduction of testosterone levels in men is associated with increased risk of atherosclerosis [2]. Results from animal models
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