Effect of Genistein Diet on Jejunum Contractility, Motility and Morphology in a Mouse Model of Diabetic Obesity

Abstract

We aimed to characterize jejunal function (contractility, motility and morphology), to better understand the intestinal dysfunction seen in the clinically relevant ob/ob mouse model of diabetes and obesity. We examined the effects of a 4-week genistein-containing diet (600 mg genistein/kg food) in female ob/ob and lean mice. Contractility (tension), of jejunum in response to incrementally increased concentrations of KCl was examined. There was no effect of genistein-diet on tension in ob/ob mice. There were no changes in jejunum total smooth muscle wall thickness, depth of inner circular smooth muscle, nor depth of outer longitudinal smooth muscle in ob/ob or lean mice fed genistein. Given the importance of the enteric nervous system in the control of local gastrointestinal functions, we evaluated total number clusters of acetylcholine receptors, AChR, via binding of α-bungarotoxin conjugated to tetramethyl-rhodamine to AChR. AChR were significantly decreased in ob/ob mice (41%, n=9, P<0.05) compared to leans (n=10), and genistein-diet reversed this. Utilizing a gastrointestinal motility monitoring system, we determined that the distance between consecutive contractile events was significantly increased by 50% in ob/ob mice (n=4, P<0.05) compared to leans (n=5), and genistein-diet reverses this. These data suggest that slowed GI transit in ob/ob mice is associated with decreased AChR, decreased contractile events/unit time, and genistein-diet ameliorates these dysfunctions. This work was supported by DAREF, SHRP, and MWU intramural funds (to L.A.)