A 2-month exposure to dietary genistein has sex-dependent effects on serum profile, cardiac protein expression, and aortic morphology in mice

Abstract

Layla Al-Nakkash, Joshua B Martin, Jennifer Cannon, Ashesh Bhakta, Lana Leung, Tom L Broderick Midwestern University, Arizona College of Osteopathic Medicine, Glendale, AZ, USA Background: The sex-dependent effects of chronic exposure to dietary genistein on cardiovascular health are poorly understood. Purpose: This study examined the effects of a genistein-containing diet on cardiovascular plasma markers, aortic morphology, blood pressure, and expression of cardioprotective proteins in male and female mice. Methods: C57BL/6J mice were fed either genistein diet (600 mg genistein/kg diet; 600G) or a genistein free diet (0G) for a period of 2 months. Results: After treatment, male and female mice fed 600G gained significantly less weight than their control counterparts fed 0G. Plasma insulin levels were significantly decreased in males only, whereas no changes in the other plasma markers were observed with 600G regardless of sex. Aortae from genistein-fed male mice demonstrated significant decreases in inner and outer luminal diameters and smooth muscle cell density. In female mice fed 600G, no changes in inner and outer luminal diameters were observed compared to female mice fed 0G, but smooth muscle cell density was significantly increased. Despite these differences in aortic morphology, no changes in arterial blood pressure were noted, regardless of sex or diet with genistein. Expression of cardiac glucose transporter type 4 (GLUT4) was increased in male hearts treated with genistein, while expression of endothelium nitric oxide synthase was significantly increased in females fed 600G compared to controls. However, no differences in inducible nitric oxide synthase protein were observed in all groups studied. Conclusion: Our data indicate that a 2-month diet with genistein results in changes in aortic morphology and expression of cardiac protein and its effects appear to be sex-dependent. Keywords: isoflavonic phytoestrogen, diet, plasma markers, cardiac effects