title: Diet-induced dyslipidemia impairs reverse cholesterol transport in hamsters.
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.
  
  
  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.
authors.affiliation: INSERM UMR915, IRT-1, 8 quai Moncousu, Nantes, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Tréguier
authors.forename: François
authors.initials: F
authors.lastname: Briand
authors.forename: Adamou
authors.initials: A
authors.lastname: Boubacar
authors.forename: Agnès
authors.initials: A
authors.lastname: André
authors.forename: Thierry
authors.initials: T
authors.lastname: Magot
authors.forename: Patrick
authors.initials: P
authors.lastname: Nguyen
authors.forename: Michel
authors.initials: M
authors.lastname: Krempf
authors.forename: Thierry
authors.initials: T
authors.lastname: Sulpice
authors.forename: Khadija
authors.initials: K
authors.lastname: Ouguerram
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001692:Biological Transport; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D006224:Cricetinae; D004032:Diet; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008647:Mesocricetus
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL