Comparison of circulating lipid profiles between fasting humans and three animal species used in preclinical studies: mice, rats and rabbits

比较空腹人类与临床前研究中使用的三种动物(小鼠、大鼠和兔子)的循环脂质谱

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Abstract

BACKGROUND: Circulating lipid metabolites are associated with many physiological and biological processes in the body, and therefore could be used as biomarkers for evaluating drug efficacy and safety in preclinical studies. However, differences in circulating lipid profiles among humans and animals often used in preclinical studies have not been fully investigated. METHODS: We performed lipidomic analysis to obtain circulating lipid profiles of fasted humans (Caucasian, n = 15) and three animal species used in preclinical studies (mice [BALB/c, n = 5], rats [Sprague-Dawley, n = 5], and rabbits [New Zealand White, n = 5]) by using liquid chromatography-mass spectrometry. RESULTS: Our data showed marked differences in lipid profiles among humans and these animal species. Furthermore, we observed that the levels of many lipid metabolites, such as poly-unsaturated fatty acid-containing cholesteryl esters, ether-type phosphoglycerolipids, and sulfatides, were significantly different (p < 0.05) by more than 10-fold in these animals (depending on the animal species) from humans. CONCLUSION: Our data could be useful while extrapolating the data on the biomarker candidates identified in preclinical studies into clinical studies.

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