| Objective GSPE is a naturally occurring antioxidant from grape seed extract, itsantioxidant power is 20 times greater than of vitamin E and 50 times greater than ofvitamin C. The study is mainly aimed at the effect and the mechanism of GSPE toimprove insulin resistance. Methods C57BL/6J Leprdb and diet-induced obese (DIO)mice were given an oral gavage of GSPE in aqueous solution(low 100mg/kg, medium200mg/kg, high 400mg/kg) for 5 weeks and 10weeks respectively. We detected theantioxidant activity, energy matabolism, antiinflammatory activity, weight, food-intake, glucose and lipid metabolism, pathology change of main organs, as wellas the TNF-αmRNA level in liver and EWAT, the PPAR-γmRNA in EWAT, and theGLUT4 protein level in lipocyte. Results GSPE can significantly induce hepaticT-AOC, SOD, GSH-Px activity of DIO mice, and reduce the hepatic MDA of db/dbmice. After 10 weeks GSPE intervention, the results obtained revealed an decreasedserum FFAs and TNF-αin DIO mice. The mRNA lever of TNF-αin liver and EWATwere significantly low in GSPE groups(100mg/kg, 200mg/kg) than obesity group.The expression of GLUT4 protein was significantly higher in GSPE group thancontrol group. The high dose of GSPE can significantly decrease the weight gain,hyperglycemia, hepatic cholesterin in db/db mice, while the low and medium dosescan evidently prevent weight gain, fatty liver, adipose tissue mass increase, andreduce hyperglycemia in DIO mice. Conclusion The study shows that GSPE iseffective in weight loss, antihyperglycemia, against insulin resistance and modulationlipid metabolism. The mechanism of GSPE on improving insulin resistance is due totheir antioxidant effects and their effects on the adipocyte, where procyanidins modifylipid synthesis, lipid degradation, glucose uptake, and adipose differentiation. GSPEin low and medium dose are better for preventing obesity induced by high fat food,and then GSPE in high dose may be better for meliorating overweight and obesity.
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