ObjectiveWe tested the effect of exercise training and genistein treatment on splenomegaly in mice fed a high-fat, high-sugar diet (HFSD).ResultsMale 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.

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.

Diets high in fat and sugar (HFSD) adversely affect bone mineralization during growth and are implicated in osteoporosis in obese adults. In this study, we assessed fracture risk in mice fed a standard diet and mice fed HFSD. We evaluated fracture risk using three‐point bending tests and comparisons of cross‐sectional geometric properties of the femur. We also investigated the effects of low‐intensity exercise and dietary genistein, an isoflavone, on fracture risk in HFSD‐fed mice. We tested the hypothesis using 50 male and 50 female C57BL/6 mice aged six weeks, which we divided into five treatment groups: lean control, HFSD control, HFSD + exercise, HFSD + genistein, and HFSD + exercise + genistein. Lean control mice were fed standard rodent chow. HFSD consisted of chow with 60% fat content and drinking water with 42 g/L sugar (55% sucrose, 45% fructose). Exercise training consisted of treadmill running for 30 min/day, 5 days/week. Genistein was given at a dose of 600 mg/kg diet. Comparisons of body mass and blood plasma revealed mice fed HFSD were obese and hyperglycemic by the end of the 12‐week treatment period. Statistical analysis of the data showed no differences in cross‐sectional geometric properties in comparisons of lean and HSFD‐fed mice (P > 0.05). However, mice fed HFSD and treated with exercise and genistein had significantly increased maximum second moments of area relative to HFSD controls (P < 0.05). Femurs of these mice also exhibited greater ultimate force during three‐point bending tests (i.e. maximum force recorded at the time of fracture) than HFSD controls (P < 0.05). Femurs of HFSD‐fed mice treated with exercise and genistein also demonstrated reduced corrected total bone fluorescence (CTBF) relative to HFSD controls (P < 0.05). CTBF quantifies advanced glycation end products (AGEs) in bone matrix. It is an indicator of fracture risk related to increased bone brittleness and reflects a reduced capacity to deform under loading. Our findings show treatment with low intensity exercise and dietary genistein increased fracture resistance in mice fed HFSD. These results suggest exercise and genistein benefit bone health in individuals with HFSD‐induced obesity.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

We previously identified significant splenomegaly in mice fed a diet high in fat and sugar (HFSD) in comparison to mice fed a standard diet. Mice fed HFSD also exhibited elevated blood plasma levels of glucose and the proinflammatory cytokine IL‐6. However, the relationship between these markers and the proliferation of immune tissue in the spleen is unclear. The white pulp of the spleen is a site of immune response and may expand when exposed to proinflammatory signaling molecules. In this study, we investigated the correlations among splenic white pulp area, plasma glucose, and plasma IL‐6. Female C57BL/6 mice aged 6 weeks were randomly divided into lean control (n=4) and HFSD (n=4) groups. HFSD consisted of chow with 60% fat content and drinking water with 42 g/L sugar (55% sucrose, 45% fructose). Treatment was administered for 12 weeks. White pulp area of the spleen was measure from histological sections stained with H&E. Mice in the HFSD group became significantly obese and hyperglycemic by the end of the study (P < 0.05). Mice fed HFSD also had significantly larger splenic white pulps than lean mice (P < 0.05). Splenic white pulp area was positively correlated with blood plasma levels of IL‐6 (r = 0.725, P < 0.05) and glucose (r = 0.686, P < 0.05). Plasma Il‐6 was also positively correlated with plasma glucose levels (r = 0.887, P < 0.01). These data support the hypothesis that HFSD is associated with histological expansion of the white pulp of the spleen that correlates with diet‐induced hyperglycemia and the expression of proinflammatory cytokines.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.