Bioactive
proanthocyanidins have been reported to have several beneficial effects on health in relation to
metabolic syndrome,
type 2 diabetes, and
cardiovascular disease. We studied the effect of grape seed
proanthocyanidin extract (GSPE) in rats fed a high fat diet (HFD). This is the first study of the effects of
flavonoids on the liver
proteome of rats suffering from
metabolic syndrome. Three groups of rats were fed over a period of 13 weeks either a chow diet (control), an HFD, or a high fat diet supplemented for the last 10 days with GSPE (HFD + GSPE). The liver
proteome was fractionated, using a Triton X-114-based two-phase separation, into soluble and
membrane protein fractions so that total
proteome coverage was considerably improved. The data from isobaric tag for relative and absolute quantitation (iTRAQ)-based nano-LC-MS/MS analysis revealed 90
proteins with a significant (p < 0.05) minimal expression difference of 20% due to
metabolic syndrome (HFD versus control) and 75
proteins due to GSPE treatment (HFD + GSPE versus HFD). The same animals have previously been studied (Quesada, H., del Bas, J. M., Pajuelo, D., Díaz, S., Fernandez-Larrea, J., Pinent, M., Arola, L., Salvadó, M. J., and Bladé, C. (2009)
Grape seed proanthocyanidins correct
dyslipidemia associated with a high-fat diet in rats and repress genes controlling lipogenesis and VLDL assembling in liver. Int. J. Obes. 33, 1007-1012), and GSPE was shown to correct
dyslipidemia observed in HFD-fed rats probably through the repression of hepatic lipogenesis. Our data corroborate those findings with an extensive list of
proteins describing the induction of hepatic glycogenesis, glycolysis, and
fatty acid and
triglyceride synthesis in HFD, whereas the opposite pattern was observed to a large extent in GSPE-treated animals. GSPE was shown to have a wider effect than previously thought, and putative targets of GSPE involved in the reversal of the symptoms of
metabolic syndrome were revealed. Some of these novel candidate
proteins such as GFPT1, CD36, PLAA (
phospholipase A(2)-activating
protein), METTL7B, SLC30A1, several G signaling
proteins, and the
sulfide-metabolizing ETHE1 and SQRDL (
sulfide-quinone reductase-like) might be considered as drug targets for the treatment of
metabolic syndrome.