Grape seed proanthocyanidins correct dyslipidemia associated with a high-fat diet in rats and repress genes controlling lipogenesis and VLDL assembling in liver.
OBJECTIVE
To determine whether proanthocyanidins can protect against dyslipidemia induced by a high-fat diet (HFD) and to address the mechanisms that underlie this hypolipidemic effect.


METHODS
Female Wistar rats were fed on a HFD for 13 weeks. They were divided into two groups, one of which was treated with a grape seed proanthocyanidin extract (25 mg kg(-1) of body weight) for 10 days. Plasma and liver lipids were measured by colorimetric and gravimetric analysis. Liver, muscle and adipose tissue were used to study the expression of genes involved in the synthesis and oxidation of fatty acids and lipoprotein homeostasis by real-time RT-PCR.


RESULTS
The administration of proanthocyanidins normalized plasma triglyceride and LDL-cholesterol (both parameters significantly increased with the HFD) but tended to decrease hypercholesterolemia and fatty liver. Gene expression analyses revealed that proanthocyanidins repressed both the expression of hepatic key regulators of lipogenesis and very low density lipoprotein (VLDL) assembling such as SREBP1, MTP and DGAT2, all of which were overexpressed by the HFD.


CONCLUSIONS
These findings indicate that natural proanthocyanidins improve dyslipidemia associated with HFDs, mainly by repressing lipogenesis and VLDL assembly in the liver, and support the idea that they are powerful agents for preventing and treating lipid altered metabolic states.
Quesada
H
H
Departament de Bioquímica i Biotecnologia, Nutrigenomics Research Group, Universitat Rovira i Virgili, Tarragona, Spain.
del Bas
J M
JM
Pajuelo
D
D
Díaz
S
S
Fernandez-Larrea
J
J
Pinent
M
M
Arola
L
L
Salvadó
M J
MJ
Bladé
C
C
D000818:Animals; D008078:Cholesterol, LDL / Q000097:blood; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D050171:Dyslipidemias / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D056604:Grape Seed Extract / Q000494:pharmacology*; D050155:Lipogenesis / Q000187:drug effects*; D008079:Lipoproteins, VLDL / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D044945:Proanthocyanidins / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D008078:Cholesterol, LDL; D004041:Dietary Fats; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D008079:Lipoproteins, VLDL; D044945:Proanthocyanidins; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; C494885:DGAT2 protein, human; D051048:Diacylglycerol O-Acyltransferase