Effects of Genistein and Exercise Training on Brain Damage Induced by a High-Fat High-Sucrose Diet in Female C57BL/6 Mice.

In recent decades, a shift in the nutritional landscape to the Western-style diet has led to an unprecedented rise in the prevalence of obesity and neurodegenerative diseases. Consumption of a healthy diet and engaging in regular physical activity represents safe and affordable approaches known to mitigate the adverse consequences of the Western diet. We examined whether genistein treatment, exercise training, and a combination treatment (genistein and exercise training) mitigated the effects of a Western diet-induced by high-fat, high-sugar (HFHS) in brain of female mice. HFHS increased the amyloid-beta (Aß) load and phosphorylation of tau, apoptosis, and decreased brain-derived neurotrophic factor (BDNF) levels. Exercise training and genistein each afforded modest protection on Aß accumulation and apoptosis, and both increased BDNF. The greatest neuroprotective effect occurred with combination treatment. BDNF and all markers of Aß accumulation, phosphorylation of tau, and apoptosis were improved with combined treatment. In a separate series of experiments, PC12 cells were exposed to high glucose (HG) and palmitate (PA) to determine cell viability with genistein as well as in the presence of tamoxifen, an estrogen receptor antagonist, to assess a mechanism of action of genistein on cell apoptosis. Genistein prevented the neurotoxic effects of HG and PA in PC12 cells and tamoxifen blocked the beneficial effects of genistein on apoptosis. Our results indicate the beneficial effects of genistein and exercise training on HFHS-induced brain damage. The benefits of genistein may occur via estrogen receptor-mediated pathways.

Urinary Biomarkers of Inflammation and Oxidative Stress Are Elevated in Obese Children and Correlate with a Marker of Endothelial Dysfunction.

Obesity is a state of chronic low-level inflammation closely associated with oxidative stress. Childhood obesity is associated with endothelial dysfunction, inflammation, and oxidative stress markers individually. This study was aimed at determining the association between the biomarkers of inflammation, oxidative stress, and endothelial dysfunction in urine samples of healthy, overweight, and obese children. Eighty-eight elementary school children aged between 6 and 10 years participated in this study. Anthropometric measurements were measured using WHO recommendations. The biomarkers of low-grade inflammation such as C-reactive protein (CRP), interleukin-6 (IL-6), and α-1-acid glycoprotein (AGP); oxidative stress markers such as 8-isoprostane and 8-hydroxy-2'-deoxyguanosine (8-OHdG); and endothelin-1 (ET-1) were analyzed in urine samples. The area under the curve (AUC) by the receiver operating characteristics (ROC) was analyzed to identify the best urinary biomarker in childhood obesity. Linear regression and Pearson correlation were analyzed to determine the association between the parameters. The obese participants have significantly increased levels of CRP, AGP, IL-6, and 8-isoprostane compared to normal-weight participants. The overweight participants had significantly increased levels of ET-1 and 8-OHdG but not the obese group compared to the NW group. The AUC for urinary CRP (AUC: 0.847, 95% CI: 0.765-0.930; p < 0.0001) and 8-isoprostane (AUC: 0.857, 95% CI: 0.783-0.932; p < 0.0001) showed a greater area under ROC curves compared to other inflammatory and oxidative markers. The urinary CRP and 8-isoprostane significantly correlated with the obesity measures (body mass index, waist circumference, and waist-to- height ratio) and ET-1, inflammatory, and oxidative markers. The increased urinary inflammatory markers and 8-isoprostane can serve as a noninvasive benchmark for early detection of the risk of developing cardiovascular disease.