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Diet‐induced dyslipidemia impairs reverse cholesterol transport in hamsters
Author(s) -
Tréguier Morgan,
Briand François,
Boubacar Adamou,
André Agnès,
Magot Thierry,
Nguyen Patrick,
Krempf Michel,
Sulpice Thierry,
Ouguerram Khadija
Publication year - 2011
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2011.02478.x
Subject(s) - dyslipidemia , reverse cholesterol transport , cholesterol , medicine , endocrinology , diabetes mellitus , lipoprotein
Eur J Clin Invest 2011; 41 (9): 921–928 Abstract Background Reverse cholesterol transport (RCT) is an anti‐atherogenic process by which cholesterol is effluxed from peripheral tissues by high‐density lipoprotein (HDL) and returned to the liver for excretion into the bile and faeces. Dyslipidemia is thought to impair RCT through higher triglyceride‐rich lipoprotein (TRL), low HDL‐cholesterol and higher activity of cholesteryl ester transfer protein (CETP), which transfers cholesteryl esters from HDL to TRL for further hepatic uptake. As CETP pathway would represent a major route in human RCT, we therefore investigated whether diet‐induced dyslipidemia impairs RCT in hamster, a CETP‐expressing species. Materials and methods Golden Syrian hamsters were fed a chow or chow+0·3% cholesterol diet over 4 weeks. Biochemical parameters and in vivo VLDL‐triglycerides secretion (Triton WR‐1339 injection) were then measured. In vitro macrophage cholesterol efflux was measured, and in vivo macrophage‐to‐faeces RCT was also assessed after an intraperitoneal injection of 3 H‐cholesterol‐labelled hamster primary macrophages. Results Cholesterol‐enriched diet increased plasma total cholesterol (144%), triglycerides (101%), VLDL‐triglycerides secretion (175%), CETP activity (44%) and reduced HDL‐cholesterol/total cholesterol ratio by 20% ( P < 0·01 vs. chow). Cholesterol‐enriched diet significantly increased hepatic total cholesterol and triglycerides by 459 and 118% and increased aortic total cholesterol content by 304%. In vitro cholesterol efflux from macrophages to plasma was significantly reduced by 25% with plasma from cholesterol‐fed hamsters. In vivo RCT experiments showed a significant 75% reduction of macrophage‐derived cholesterol faecal excretion in cholesterol‐fed hamsters. Conclusions Overall, these data demonstrate that diet‐induced dyslipidemia severely impairs in vivo RCT in hamsters.