Bone Strength Is Improved with Genistein Treatment in Mice with Diet-Induced Obesity.

BACKGROUND: High caloric intake of saturated fat and refined sugars accelerates the development of obesity and diabetes and increases bone fracture risk. Some evidence suggests that consumption of a diet rich in phytoestrogens like genistein has the potential to strengthen bone biomechanical properties. Its bone-strengthening properties may mitigate fracture risk associated with metabolic conditions like obesity and diabetes, especially when combined with exercise. OBJECTIVE: In this study, we test the effects of genistein, exercise training, and combination treatment on biomechanical properties of cortical bone in mice fed a high-fat, high-sugar (HFHS) diet. METHODS: Eighty C67BL6 mice (40 females, 40 males) aged 6 wk were treated for 12 wk with an HFHS diet containing 60% fat and drinking water with 4.2 g/L sugar (55% sucrose, 45% fructose). Subgroups of the mice were also treated with genistein and/or moderate exercise (treadmill running). Genistein was incorporated into the HFHS diet (600 mg genistein/kg HFHS) and exercise was performed daily for 30 min, 5 d/wk (n = 10 females, 10 males per group). Three-point bending mechanical testing and quantitative fluorescence microscopy were conducted on femurs to measure bone strength and matrix quality. RESULTS: Mechanical testing revealed HFHS-fed mice treated with genistein, either alone or combined with exercise, had femurs that exhibited increased postyield displacement and reduced stiffness during 3-point bending in comparison with mice only treated with the HFHS diet. Femurs of genistein-treated mice also exhibited greater ultimate force required to achieve fracture. Quantitative fluorescence showed genistein reduced advanced glycation end product accumulation in bone matrix. Exercise treatment alone had no effect. CONCLUSIONS: Treatment with genistein, either alone or in combination with exercise, improves fracture resistance in mice fed an HFHS diet by improving bone matrix quality and increasing bone strength.

High-fat, high-sugar diet induces splenomegaly that is ameliorated with exercise and genistein treatment.

OBJECTIVE: We tested the effect of exercise training and genistein treatment on splenomegaly in mice fed a high-fat, high-sugar diet (HFSD). RESULTS: Male and female C57BL6 mice fed HFSD containing 60% fat along with drinking water containing 42 g/L sugar (55% sucrose/45% fructose) for 12 weeks exhibited significant obesity, hyperglycemia, and elevated plasma IL-6 levels. This was accompanied by splenomegaly characterized by spleen weights 50% larger than mice fed standard chow (P < 0.05) with enlarged rad and white pulps. Mice fed HFSD and treated with a combination of exercise (30 min/day, 5 days/week) and genistein (600 mg genistein/kg diet) had reduced spleen weight (P < 0.05). The decrease in spleen weight was associated with a significant improvement in red-to-white pulp area ratio and plasma glucose and IL-6 (P < 0.05). Our findings indicate that reversal of splenomegaly by regular exercise and genistein treatment may be important in the clinical management of HFSD-induced obesity.