Testosterone deficiency accelerates early stage atherosclerosis in miniature pigs fed a high-fat and high-cholesterol diet: urine 1H NMR metabolomics targeted analysis

被引:0
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作者
Liqun Deng
Danting Fu
Liang Zhu
Junjie Huang
Yun Ling
Zhaowei Cai
机构
[1] Academy of Chinese Medical Sciences,Laboratory Animal Research Center
[2] Zhejiang Chinese Medical University,Institute of Comparative Medicine
[3] Zhejiang Chinese Medical University,Department of Experimental Animals
[4] Zhejiang Academy of Traditional Chinese Medicine,undefined
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关键词
Atherosclerosis; Miniature pigs; H-NMR metabolomics; High-fat and high cholesterol diet; Testosterone deficiency;
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摘要
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.
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页码:1245 / 1255
页数:10
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