Raul Y. Dagda

Green tea polyphenols benefits body composition and improves bone quality in long-term high-fat diet-induced obese rats.

This study investigates the effects of green tea polyphenols (GTPs) on body composition and bone properties along with mechanisms in obese female rats. Thirty-six 3-month-old Sprague Dawley female rats were fed either a low-fat (LF) or a high-fat (HF) diet for 4 months. Animals in the LF diet group continued on an LF diet for additional 4 months, whereas those in the HF diet group were divided into 2 groups: with GTP (0.5%) or without in drinking water, in addition to an HF diet for another 4 months. Body composition, femur bone mass and strength, serum endocrine and proinflammatory cytokines, and liver glutathione peroxidase (GPX) protein expression were determined. We hypothesized that supplementation of GTP in drinking water would benefit body composition, enhance bone quality, and suppress obesity-related endocrines in HF diet-induced obese female rats and that such changes are related to an elevation of antioxidant capacity and a reduction of proinflammatory cytokine production. After 8 months, compared with the LF diet, the HF diet increased percentage of fat mass and serum insulin-like growth factor I and leptin levels; reduced percentage of fat-free mass, bone strength, and GPX protein expression; but had no effect on bone mineral density and serum adiponectin levels in the rats. Green tea polyphenol supplementation increased percentage of fat-free mass, bone mineral density and strength, and GPX protein expression and decreased percentage of fat mass, serum insulin-like growth factor I, leptin, adiponectin, and proinflammatory cytokines in the obese rats. This study shows that GTP supplementation benefited body composition and bone properties in obese rats possibly through enhancing antioxidant capacity and suppressing inflammation.

Alcohol-induced One-carbon Metabolism Impairment Promotes Dysfunction of DNA Base Excision Repair in Adult Brain

Background: DNA repair dysfunction leads to genomic instability and neuron death. Results: Long term alcohol exposure results in reduced DNA repair, increased DNA damage, and neuron death in adult brain. Conclusion: Long term alcohol exposure in adult brain promotes genomic instability mediated by impairment in one-carbon metabolism. Significance: This is the first demonstration of alcohol-induced genomic instability in brain. The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr+/− mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain.

Protective actions of green tea polyphenols and alfacalcidol on bone microstructure in female rats with chronic inflammation.

This study investigated the effects of green tea polyphenols (GTP) and alfacalcidol on bone microstructure and strength along with possible mechanisms in rats with chronic inflammation. A 12-week study using a 2 (no GTP vs. 0.5%, w/v GTP in drinking water)×2 (no alfacalcidol vs. 0.05 μg/kg alfacalcidol orally, 5×/week) factorial design was employed in lipopolysaccharide (LPS)-administered female rats. A group receiving placebo administration was used to compare with a group receiving LPS administration only to evaluate the effect of LPS. Changes in tibial and femoral microarchitecture and strength of femur were evaluated. Difference in expression of tumor necrosis factor-α (TNF-α) in proximal tibia using immunohistochemistry was examined. Compared to the placebo group, the LPS-administered-only group had significantly lower femoral mass, trabecular volume, thickness and number in proximal tibia and femur, and lower periosteal bone formation rate in tibial shafts but had significantly higher trabecular separation and osteoclast number in proximal tibia and eroded surface in endocortical tibial shafts. Both GTP and alfacalcidol reversed these LPS-induced detrimental changes in femur, proximal tibia and endocortical tibial shaft. Both GTP and alfacalcidol also significantly improved femoral strength, while significantly suppressed TNF-α expression in proximal tibia. There were significant interactions in femoral mass and strength, trabecular separation, osteoclast number and TNF-α expression in proximal tibia. A combination of both showed to sustain bone microarchitecture and strength. We conclude that a protective impact of GTP and alfacalcidol in bone microarchitecture during chronic inflammation may be due to a suppression of TNF-α.

Green Tea Polyphenols and 1-α-OH-Vitamin D3 Attenuate Chronic Inflammation-Induced Myocardial Fibrosis in Female Rats

Studies have suggested that 1-α-OH-vitamin D₃ and green tea polyphenols (GTPs) are promising dietary supplements for mitigating chronic inflammation-induced fibrosis of vessels because of their anti-inflammatory properties. This study evaluated (1) the impact of 1-α-OH-vitamin D₃ on myocardial fibrosis in female rats with chronic inflammation and (2) if 1-α-OH-vitamin D₃ and GTPs have an additive or synergistic effect to attenuate myocardial fibrosis in these female rats. A 3-month study of a 2 (no 1-α-OH-vitamin D₃ vs. 0.05 μg/kg 1-α-OH-vitamin D₃, five times per week) ×2 (no GTPs vs. 0.5% GTPs in drinking water) factorial design in lipopolysaccharide (LPS)-administered female rats was performed. Additionally, a group receiving placebo administration was used to compare with a group receiving LPS administration only to evaluate the effect of LPS. Massons Trichrome staining evaluated myocardial fibrosis in coronary vessels and surrounding myocardium. Spleen cyclooxygenase-2 mRNA expression was determined by real-time polymerase chain reaction. Total lipid profiles were also determined. Whole blood was used for differential cell counts. Data were analyzed by two-way analysis of variance followed by mean separation procedures. At 3 months LPS administration induced myocardial fibrosis in vessels and surrounding myocardium, spleen cyclooxygenase-2 mRNA expression, and elevated leukocyte counts, whereas both 1-α-OH-vitamin D₃ administration and GTPs supplementation significantly attenuated these pro-inflammatory events. The inhibitory effects of 1-α-OH-vitamin D₃ and GTPs seem to be an individual effect, instead of an additive or synergistic effect. 1-α-OH-vitamin D₃ and GTPs lowered red blood cell counts, hematocrit, and hemoglobin. Neither 1-α-OH-vitamin D₃ nor GTPs affected lipid profiles. In summary, both 1-α-OH-vitamin D₃ administration and GTPs supplementation mitigate myocardial fibrosis through suppression of a chronic inflammation innate immune response.

Effects of Martial Arts Exercise on Body Composition, Serum Biomarkers and Quality of Life in Overweight/Obese Premenopausal Women: A Pilot Study

Various exercise interventions have been shown to benefit weight control and general health in different populations. However, very few studies have been conducted on martial arts exercise (MAE). The objective of this pilot study is to evaluate the efficacy of 12 weeks of MAE intervention on body composition, serum biomarkers and quality of life (QOL) in overweight/obese premenopausal women. We found that subjects in the MAE group did not lose body weight, while they significantly decreased fat-free mass and muscle mass as compared to those in the control group, who demonstrated an increase in these parameters. The MAE group demonstrated an increase in serum IGF-I concentration, but no change in others. MAE may be a feasible and effective approach to improve body composition and QOL in overweight/obese premenopausal women. Our study underscores the need for further studies using larger samples to establish possible benefits of MAE in various populations.