Objective To explore the effect of soy isoflavone on obesity in the light of hypothalamus and peripheral orexigenic gene regulation.Methods Fifty-four female rats were randomly assigned to 6 groups:one sham-operated group (SHAM),one ovariectomized (OVX)control group,three OVX groups fed with 400 ppm(L-SI),1 200 ppm(M-SI)and 3 600 ppm(H-SI)isoflavone respectively,and one OVX group receiving 0.45 ppm diethylstilbestrol(EC).All rats were allowed to take high-fat diet for 4 weeks.Some neuropeptides were measured by RT-PCR.These neuropeptides included NPY,pro-opiomelanocortin(POMC),cocaine and amphetamine regulated transcript(CART),orexin,melanin-concentrating hormone(MCH),melanin-concentrating hormone precursor(P-MCH),ghrelin,and leptin.Results Compared with the OVX control group,the body weight and food intake in the H-SI group were reduced significantly and there was a significant dose-dependent manner in the 3 isoflavone groups.The results of RT-PCR showed that the NPY level in the 3 isoflavone groups was significantly increased and the POMC/CART gene expression decreased significantly in rats’ hypothalamus compared with that in the OVX control group.However,the expression of orexin,MCH and P-MCH had no change.The peripheral grelin mRNA expression was higher in the 3 isoflavone groups,while leptin gene expression in the fat was not consistent.Conclusions This research showed that isoflavone could prevent obesity induced by high-fat diet and ovariectomy through regulating hypothalamus and peripheral orexigenic gene expressions associated with food intake. Objective To explore the effect of soy isoflavone on obesity in the light of hypothalamus and peripheral orexigenic gene regulation. Methods Fifty-four female rats were randomly assigned to 6 groups: one sham-operated group (SHAM), one ovariectomized (OVX) control group , three OVX groups fed with 400 ppm (L-SI), 1 200 ppm (M-SI) and 3 600 ppm (H-SI) isoflavone respectively, and one OVX group received 0.45 ppm diethylstilbestrol (EC) To take a high-fat diet for 4 weeks. Whole neuropeptides were measured by RT-PCR. These neuropeptides included NPY, pro-opiomelanocortin (POMC), cocaine and amphetamine regulated transcript (CART), orexin, melanin-concentrating hormone melanin-concentrating hormone precursor (P-MCH), ghrelin, and leptin. Results Compared with the OVX control group, the body weight and food intake in the H-SI group were reduced significantly and there was a significant dose-dependent manner in the 3 isoflavone groups.The results of RT-PCR showed that the NPY level in the 3 is oflavone groups was significantly increased and the POMC / CART gene expression decreased significantly in rats’ hypothalamus compared with that in the OVX control group. Despite, the expression of orexin, MCH and P-MCH had no change. in the 3 isoflavone groups, while leptin gene expression in the fat was not consistent. Conclusions This research showed that isoflavone could prevent obesity induced by high-fat diet and ovariectomy through regulating hypothalamus and peripheral orexigenic gene expressions associated with food intake.