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

Abstract

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.

Sex‐Dependent Effects of Dietary Genistein on Echocardiographic Profile and Cardiac GLUT4 Signaling in Mice

“…We first determined total GLUT4 content in hearts from mice fed genistein for a period of 4 weeks. As shown in Figure 3 , feeding mice a genistein-containing diet increased the expression of total GLUT4, confirming our earlier findings [ 17 ]. Western blot analysis revealed that cardiac GLUT4 expression was significantly increased in both male (1.51-fold from 0.79 ± 0.25 ( n = 10) to 1.18 ± 0.51 ( n = 9), P < 0.05) and female (1.76-fold from 0.52 ± 0.13 ( n = 10) to 0.92 ± 0.29 ( n = 10), P < 0.05) mice fed 600 G. Interestingly, male control mice (0 GM) had significantly greater GLUT4 expression (1.52-fold) compared to females control counterparts.…”

“…However, in addition to these differences in plasma insulin and glucose to genistein treatment, which makes it difficult to accurately assess how genistein affects glucose metabolism, we have previously demonstrated that this phytoestrogen administered for a period of 2 months increases the expression of the glucose transporter GLUT4 in male murine cardiac tissue [ 17 ]. We further confirm this finding in this current study with the significant increase in the expression of total protein GLUT4 content following genistein treatment.…”

“…Standard western blot techniques, as described previously [ 17 ], were utilized to measure the following proteins: GLUT4 (~40–48 kD), iNOS (~130 kD), eNOS (~130 kD), SYNIP (~62 kD), Akt (~60 kD), AMPK (~62 kD), and MEF2a (~55 kD). Total protein concentration of whole heart tissue was determined (Pierce, Rockford IL).…”

“…Extending treatment with genistein to a period of 2 weeks in the ovariectomized rat resulted in decreased body weight and aortic pulse pressure, induction of a bradycardic effect, and decreased insulin resistance [ 16 ]. In the absence of ovariectomy (i.e., in intact mice), feeding mice a genistein-containing diet for a period of 8 weeks improved cardiovascular risk factors and aortic reactivity and produced favorable effects on glucose metabolism by increasing the expression of GLUT4 in the myocardium [ 17 ]. Taken together, our previous studies indicate that supplemental genistein, regardless of the route of administration, has benefits on cardiovascular function.…”

Dietary Genistein Influences Number of Acetylcholine Receptors in Female Diabetic Jejunum

“…The genistein-containing diet (Gen) was purchase from Dyets Inc. (Bethlehem, PA) and contained 600 mg genistein/kg diet. The composition of the genistein diet has been published previously [ 9 , 13 , 14 ]. Food and water were provided ad libitum.…”