BH4 activates CaMKK2 and rescues the cardiomyopathic phenotype in rodent models of diabetes.

Diabetic cardiomyopathy (DCM) is a major cause of mortality/morbidity in diabetes mellitus patients. Although tetrahydrobiopterin (BH4) shows therapeutic potential as an endogenous cardiovascular target, its effect on myocardial cells and mitochondria in DCM and the underlying mechanisms remain unknown. Here, we determined the involvement of BH4 deficiency in DCM and the therapeutic potential of BH4 supplementation in a rodent DCM model. We observed a decreased BH4:total biopterin ratio in heart and mitochondria accompanied by cardiac remodeling, lower cardiac contractility, and mitochondrial dysfunction. Prolonged BH4 supplementation improved cardiac function, corrected morphological abnormalities in cardiac muscle, and increased mitochondrial activity. Proteomics analysis revealed oxidative phosphorylation (OXPHOS) as the BH4-targeted biological pathway in diabetic hearts as well as BH4-mediated rescue of down-regulated peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC-1α) signaling as a key modulator of OXPHOS and mitochondrial biogenesis. Mechanistically, BH4 bound to calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) and activated downstream AMP-activated protein kinase/cAMP response element binding protein/PGC-1α signaling to rescue mitochondrial and cardiac dysfunction in DCM. These results suggest BH4 as a novel endogenous activator of CaMKK2.

The Effects of 12 Weeks of a Combined Exercise Program on Physical Function and Hormonal Status in Elderly Korean Women.

Aging causes a decline in physical function and hormonal balance. Exercise can improve these parameters. However, the beneficial effects of a combined exercise program (Korean dance and yoga) on physical function and hormonal status in elderly women remain unknown. This study aims to investigate the effects of a 12-week combined exercise program on balance, flexibility, muscle strength, and hormonal status in elderly Korean women. Twenty-five healthy elderly women were recruited and randomly divided into the control (CON) and exercise (EXE) groups. The EXE group underwent the combined exercise program (60 min/day and 3 times/week) for 12 weeks. The two groups did not differ in body weight, lean body mass, fat mass, body fat percentage, or body mass index at baseline or in the changes following the experimental conditions. A significant time × group interaction was detected for anterior and posterior dynamic balance, static balance, and growth hormone (GH). After the combined exercise program, anterior dynamic balance, posterior dynamic balance, static balance, flexibility, muscle strength, GH, dehydroepiandrosterone-sulfate, and estrogen significantly increased in the EXE group compared to the CON group. In conclusion, the combined exercise program contributed to improvements in overall health, including physical function and hormonal status, in elderly Korean women.

Resistance Exercise Training Attenuates the Loss of Endogenous GLP-1 Receptor in the Hypothalamus of Type 2 Diabetic Rats.

The aim of this study was to investigate the effects of resistance exercise training on hypothalamic GLP-1R levels and its related signaling mechanisms in T2DM. The animals were separated into three groups: a non-diabetic control (CON), diabetic control (DM), and diabetic with resistance exercise (DM + EXE) group. The resistance exercise training group performed ladder climbing (eight repetitions, three days per week for 12 weeks). Body weight was slightly lower in the DM + EXE group than the DM group, but difference between the groups was not significant. Food intake and glucose were significantly lower in the DM + EXE group than in the DM group. The blood insulin concentration was significantly higher and glucagon was significantly lower in the DM + EXE group. The DM + EXE group in the hypothalamus showed significant increases in GLP-1R mRNA, protein kinase A (PKA), glucose transporter 2 (GLUT2), and protein kinase B (AKT) and significant decrease in protein kinase C-iota (PKC-iota). Antioxidant enzymes and apoptosis factors were significantly improved in the DM + EXE group compared with the DM group in the hypothalamus. The results suggest that resistance exercise contributes to improvements the overall health of the brain in diabetic conditions.

Yoga training improves metabolic parameters in obese boys.

Yoga has been known to have stimulatory or inhibitory effects on the metabolic parameters and to be uncomplicated therapy for obesity. The purpose of the present study was to test the effect of an 8-week of yoga-asana training on body composition, lipid profile, and insulin resistance (IR) in obese adolescent boys. Twenty volunteers with body mass index (BMI) greater than the 95th percentile were randomly assigned to yoga (age 14.7±0.5 years, n=10) and control groups (age 14.6±1.0 years, n=10). The yoga group performed exercises three times per week at 40~60% of heart-rate reserve (HRR) for 8 weeks. IR was determined with the homeostasis model assessment of insulin resistance (HOMA-IR). After yoga training, body weight, BMI, fat mass (FM), and body fat % (BF %) were significantly decreased, and fat-free mass and basal metabolic rate were significantly increased than baseline values. FM and BF % were significantly improved in the yoga group compared with the control group (p<0.05). Total cholesterol (TC) was significantly decreased in the yoga group (p<0.01). HDL-cholesterol was decreased in both groups (p<0.05). No significant changes were observed between or within groups for triglycerides, LDL-cholesterol, glucose, insulin, and HOMA-IR. Our findings show that an 8-week of yoga training improves body composition and TC levels in obese adolescent boys, suggesting that yoga training may be effective in controlling some metabolic syndrome factors in obese adolescent boys.