Tikrit Journal of Pure Science

T he current study was constructed to evaluate the efficacy of grape seed extracts (GSE) in management of obesity induced by high fat diet (HFD)-induced obesity in rats through assessment of the serum leptin, adiponectin, and resistin. Experimental rats were divided into three groups: G:1 (healthy control), G:2 (obese control), G:3 (received100 mg/kg of GSE), after 7 weeks, serum leptin, adiponectin, and resistin levels were measured in all groups. Results in present study showed a significant (P<0.01) increase of serum leptin, and resistin levels in obese rats G2 in comparison to the control healthy rats G1 (39.35±1.07 vs 7.48±0.6), (48.84±3.73 vs 31.43 ± 2.02) respectively. The level of serum leptin, and resistin in obese rats decreased significantly in G3 (P < 0.01) when received GSE 100 mg/kg body weight for 7 weeks in regard to G2 (30.46 ± 0.93 vs 39.35 ± 1.07), (42.23±1.21vs48.84±3.73), whereas significant decrease in serum adiponectin level in obese rats G2 to G1 (4.8793 ± 0.5040 vs 9.245 ± 0.8794). After treatment with 100 mg/kg GSE, the level of adiponectin decresed in G3 compared with G2 (6.1220 ±0.6330 vs 4.8793± 0.5040). Conclusions : The results show that, the phenolic extracts of grape seed could reduce serum leptin, and resistin levels and increase adiponectin in HFD induced obesity in rats.


Introduction
Obesity has reached truly epidemic proportions worldwide and has become one of the most prevalent health problems that our world currently faces [1].Grape seed (Vitisvinifera Linn.) is one of the most important bioflavonoid having great therapeutic potential, it is represents a source of various vitamins, minerals, and polyphenols including flavonoids, proanthocyanidins, and procyanidins.GSE exhibits potent intestinal alpha glucosidase and pancreatic αamylase inhibitors [2,3]. .The present study was therefore conducted to determine the effect of GSE the levels of leptin, adiponectin, and resistin in HFD induced obesity in rats.

Materials and Methods
Animals (adult wister albino) rats weighing 120-150g were purchased from the disease-free stock of the animal house of the Faculty of Veterinary Medicine, University of Tikrit, animals of control group were feed on a HFD and water adlibitum.The animals were divided into 3 groups each group consists of 10 animals: G 1: Consists of rats treated with normal diet .G2: Obese group received HFD for 49 days.G 3: Obese group received100 mg/kg of GSE orally three times per week for 7 weeks [4].High-Fat Diet Formula: HFD that consists of 58% fat, 25% protein and 17% carbohydrate, lard (13%), cholesterol (1%), vitamin, and minerals (0.6%) as a percentage of total kcal ad libitum, respectively, was administered every [5].
. Food intake was calculated every day and bodyweight was measured once in every two days.Phenolic extraction of grape seeds (500 g) of the dry powder wall nuts were defatted by washing five times with n-hexane(1L) at (60°C), then it was macerated with (800mL) of acetic acid (2% v/v), the mixture were placed in conical flask volume (2000mL) and put in water bath (60°C) for 8 hrs, then the extraction process done by reflex condenser.The mixture was heated at 50°C (water bath) for 15 min and left to cool.The suspension was filtered by Buchner funnel by Whatman No.1 filter paper and by the use of vacuum pump.The precipitate was canceled and the filtrate volume was measured.npropanol was added in to filtrate with the same volume of filtrate.Then (NaCl) was added until to become solution super saturated.Then, it was evaporator by using rotary evaporator until drying [5].

Discussion
In the present study, the treatment of G3 with the GSE elecited significant decrease in serum leptin and resistin, whereas increse in adiponectin level.Adiponectin is an antiatherogenic agent that attenuates cardiovascular risk which may be attributed to its anti-inflammatory properties.It inhibits endothelial adhesion and dysfunction, because it suppresses the expression of "LDL scavenger receptors" on macrophages, thus lowering LDL uptake and plaque formation [6,7].Contrary to leptin and resistin, adiponectin improves insulin sensitivity, and its concentration in serum is inversely proportional to visceral adiposity level.Obese patients with inherited hypo adiponectinemia developed a pattern of leptin resistance followed by insulin resistance, dyslipidemia and cardiovascular disease [8,9].
Resistin is implicated in pathogenesis of insulin resistance by induction of 50 AMP-activated kinasedependent protein leading to increase of gluconeogenesis through glucose-6-phosphatase, phosphoenolpyruvate carboxykinase, elevation of fatty acid esterification of triglycerides and initiation of fatty acids biosynthesis via acetyl -CoA carboxylase-1 as well.Thus, interestingly GSE treatment decreased glucose-6-phosphatase and phospho enolpyruvate carboxy kinase gene expression in C57BL/6 mice fed high-fat diet, which reduced gluconeogenesis and improved insulin sensitivity, like metformin's mode of action in the treatment of insulin resistance [10,11].

Conclusion
This study showed that GSE can significantly reduce serum leptin, and resistin with an increase in adiponectin level in HFD induced obesity in rats.

Figure 1 :
Figure 1: BMI of rats treated with grape seeds extract