Grape seed extract: How to be fat and healthy?

Lipidomics Gateway (28 October 2009) [doi:10.1038/lipidmaps.2009.30]

Proanthocyanidins from grape seeds reduce the atherogenic risk associated with obesity, by repressing genes involved in the secretion of very low density lipoprotein.

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Metabolic syndrome, associated with abdominal obesity, is a cluster of metabolic disorders that raise the risk of cardiovascular disease. High levels of serum triglycerides and an altered lipoprotein profile form a characteristic atherogenic dyslipidemia that often occurs with the condition. Proanthocyanidins are a group of flavonoids found in grape seeds or concentrated red grape juice, and are known to improve serum lipid profiles of rodents and humans, as well as exerting antioxidant effects. Now, Josepa Salvadó and colleagues have shown that grape seed proanthocyanidin extracts (GSPE) can prevent the dyslipidemia caused by a high fat diet in rats. Their report in the International Journal of Obesity suggests that eating more proanthocyanidin-rich foods might counteract the increased risk of heart attack that is associated with a high-fat diet (HFD), obesity and metabolic syndrome.

Female Wistar rats fed with a HFD for 13 weeks were significantly heavier than controls and had increased liver mass. Hepatic levels of triglycerides, cholesterol and total lipids were all raised by the HFD. After this initial period, one group of rats was given an oral GPSE treatment for 10 days, which did not reduce the level of total plasma cholesterol, or have much effect on the obesity. Nevertheless, GPSE did substantially reduce the atherogenic risk index determined by the ratio of cholesterol associated with high density lipoprotein (HDL-C), compared to that with low density lipoprotein (LDL-C), as well as lowering plasma triglyceride levels.

The levels of circulating lipids and lipoproteins are controlled by the liver, so the authors examined the effect of the HFD and GSPE treatment on hepatic gene expression. They used reverse transcription-PCR to measure the expression of key genes involved in cholesterol metabolism, fatty acid oxidation, assembly of very low density lipoproteins (VLDL) and regulation of hepatic lipid metabolism. The expression profile of HFD rats, which was indicative of active triglyceride synthesis and assembly of VLDL as well as impaired fatty acid oxidation, was consistent with the fatty liver in these animals. Treatment with GPSE significantly repressed expression of the genes encoding the transcription factor SREBP1, the triglyceride synthesis protein DGAT2, and a protein involved in VLDL assembly, MTP. Together, these proteins are key regulators of VLDL synthesis and secretion.

GSPE treatment did not affect the expression of genes involved in cholesterol metabolism. It also did not modify LDL receptor expression, indicating that GSPE reduces LDL-C by reducing VLDL secretion, leading to lower LDL production, rather than by increasing uptake of LDL by the liver. Neither the HFD nor GSPE affected the expression of lipoprotein lipase.

This study is consistent with reports of how GPSE targets lipid metabolism genes in normolipidemic rats, but it is the first to show that GSPE can improve dyslipidemia associated with a high-fat diet. Thus, increasing the intake of foods rich in proanthocyanidins might be a strategy to reduce the risk of cardiovascular disease associated with obesity.

Emma Leah