Effects of trans-10,cis-12 conjugated linoleic acid on cholesterol metabolism in hypercholesterolaemic hamsters.
BACKGROUND
Conjugated linoleic acid (CLA) has received great attention in recent years because of its pleiotropic biological activities, but considerably fewer studies have been published addressing its role in serum lipids and atherosclerosis compared to other topics covered.


OBJECTIVE
The aim of the present study was to assess the effects of the trans-10,cis-12 isomer of CLA on cholesterolaemia and on several metabolic pathways involved in cholesterol metabolism in hamsters.


METHODS
Animals were fed atherogenic diets supplemented with 0.5% linoleic acid, 0.5% trans-10,cis-12 CLA or 1.0% trans-10,cis-12 CLA, for 6 weeks. Serum lipoproteins were separated by FPLC. Cholesterol in serum and liver, as well as triacylglycerols and phospholipids in liver were assessed by spectrophotometry. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR), acyl-coenzyme A:cholesterol acyltransferase (ACAT) and cholesteryl ester hydrolase (CEH) activities were measured by radiometry, and LDL receptors were determined by Western blot.


RESULTS
trans-10,cis-12 CLA feeding did not modify food intake nor final body weight. Although serum total cholesterol remained unchanged, when cholesterol fractions were analyzed a significant decrease in VLDL-cholesterol was observed in CLA-fed animals, without changes in HDL-cholesterol or LDL-cholesterol. trans-10,cis-12 CLA decreased cholesterol ester content and increased free cholesterol in liver. The activity of HMGCoAR was not modified. In contrast, ACAT activity was reduced by both CLA doses and CEH was increased by the high CLA dose. LDL receptors were significantly reduced by trans-10,cis-12 feeding when expressed as arbitrary units per mg of protein, however, the total receptor mass remained unchanged.


CONCLUSIONS
These results suggest that, under the present experimental conditions, trans-10,cis-12 CLA feeding reduces cholesterol esterification in liver and decreases the minority serum VLDL-cholesterol fraction, but it does not show a hypocholesterolaemic effect. A dose-response effect was not observed.
Navarro
Virginia
V
Dept. of Nutrition and Food Science, Faculty of Pharmacy, University of País Vasco, Paseo de la Universidad 7, 01006 Vitoria, Spain.
Macarulla
M Teresa
MT
Fernández-Quintela
Alfredo
A
Rodríguez
Víctor M
VM
Simón
Edurne
E
Portillo
María P
MP
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood*; D002853:Chromatography, Liquid; D006224:Cricetinae; D004036:Diet, Atherogenic; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects / Q000378:metabolism; D006937:Hypercholesterolemia / Q000378:metabolism*; D044243:Linoleic Acids, Conjugated / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D010743:Phospholipids / Q000378:metabolism; D011874:Radiometry; D013053:Spectrophotometry; D002787:Sterol Esterase / Q000187:drug effects / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000187:drug effects / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D044243:Linoleic Acids, Conjugated; D010743:Phospholipids; D014280:Triglycerides; C496197:trans-10,cis-12-conjugated linoleic acid; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase