Genistein supplementation prevents weight gain but promotes oxidative stress and inflammation in the vasculature of female obese ob/ob mice

Obesity, a state of chronic low-grade inflammation, is strongly associated with the development of hypertension and diabetes. Superoxide, a free radical elevated in obese individuals, promotes hypertension through scavenging the endogenous vasodilator nitric oxide. The hypothesis was a genistein-enriched diet would promote weight loss and reduce oxidative stress and inflammation in the vasculature of intact female ob/ob mice. Aortas and mesenteric arteries were isolated from female ob/ob mice fed genistein-free (0 mg genistein/kg diet; n = 6), standard chow (200–300 mg genistein/kg diet; n = 11) or genistein-enriched (600 mg genistein/kg diet; n = 9) diets for 4 weeks. Sections of isolated vessels were labeled with the superoxide indicator dihydroethidium and fluorescence was measured by confocal microscopy. Protein expression of the inflammatory marker inducible nitric oxide synthase (iNOS) was measured in the perivascular adipose tissue (PVAT) surrounding each vessel and plasma concentrations of superoxide dismutase (SOD) were quantified. Genistein-enriched diet promoted less weight gain compared to animals fed standard chow (P = .008). Standard chow promoted increased superoxide in the aorta (P = .030) and mesenteric arteries (P = .024) compared to a diet devoid of genistein. At all tested concentrations, genistein significantly increased iNOS expression in mesenteric artery PVAT (vs. standard chow, P < .001; vs. genistein-enriched, P = .002) and tended to increase iNOS within the aortic PVAT (standard chow, P = .075) compared to the genistein-free group. Plasma SOD activity was significantly downregulated in genistein-enriched animals as compared to those fed a genistein-free diet (P = .028). In summary, although genistein prevents weight gain, it promotes vascular oxidative stress and inflammation in obese ovarian-intact female mice.