title: Genistein supplementation prevents weight gain but promotes oxidative stress and inflammation in the vasculature of female obese ob/ob mice.
abstract: 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 (0mg genistein/kg diet; n=6), standard chow (200-300mg genistein/kg diet; n=11) or genistein-enriched (600mg genistein/kg diet; n=9) diets for 4weeks. 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.
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ.
authors.forename: Anna
authors.initials: A
authors.lastname: Simperova
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ.
authors.forename: Layla
authors.initials: L
authors.lastname: Al-Nakkash
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ.
authors.forename: James J
authors.initials: JJ
authors.lastname: Faust
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ; School of Nutrition and Health Promotion, Arizona State University, Tempe, AZ. Electronic address: Karen.Sweazea@asu.edu.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Sweazea
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000187:drug effects; D004032:Diet; D005260:Female; D019833:Genistein / Q000008:administration & dosage* / Q000009:adverse effects; D006973:Hypertension; D007249:Inflammation / Q000139:chemically induced*; D008638:Mesenteric Arteries / Q000737:chemistry / Q000187:drug effects; D051379:Mice; D008820:Mice, Obese; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D009765:Obesity; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000097:blood; D013481:Superoxides / Q000032:analysis; D014652:Vascular Diseases / Q000139:chemically induced*; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D013481:Superoxides; D019833:Genistein; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase
keywords: Arteries; Genistein; Obese mouse; Obesity; Oxidative stress; Reactive oxygen species; Superoxide