Feeding Obese Diabetic Mice a Genistein Diet Induces Thermogenic and Metabolic Change

Obesity is associated with elevated plasma levels of glucocorticoids and reduced levels of thyroid hormones, both known to effect food intake and energy expenditure. Furthermore, tissue specific glucocorticoid metabolism is altered in obesity, increasing insulin resistance and cardiometabolic risk. The goal of this study was to examine whether these metabolic disturbances can be prevented with the isoflavone genistein in the ob/ob mouse, a model that resembles the phenotype in human obesity. Male ob/ob mice, aged 5 weeks, were fed either a genistein-rich diet (600 mg/kg) or a genistein-free diet for 4 weeks. ob/ob mice weighed 70% more than lean controls. While there was no effect of genistein on body weight, food consumption during weeks 3 and 4 was significantly increased in genistein-fed mice. This was associated with increases in body temperature and plasma levels of triiodothyronine (T₃), suggesting a thermogenic effect. The hypercorticosteronism observed in the ob/ob mouse was reduced with genistein treatment. This effect was accompanied by a decrease in protein expression of renal 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) without changes in hepatic 11β-HSD1. Our results suggest that a diet containing genistein can have beneficial effects on energy expenditure, T₃ production, and corticosterone status in the ob/ob mouse model of obesity.