Ryuichi Ajisaka

Testosterone and DHEA activate the glucose metabolism-related signaling pathway in skeletal muscle

Circulating dehydroepiandrosterone (DHEA) is converted to testosterone or estrogen in the target tissues. Recently, we demonstrated that skeletal muscles are capable of locally synthesizing circulating DHEA to testosterone and estrogen. Furthermore, testosterone is converted to 5alpha-dihydrotestosterone (DHT) by 5alpha-reductase and exerts biophysiological actions through binding to androgen receptors. However, it remains unclear whether skeletal muscle can synthesize DHT from testosterone and/or DHEA and whether these hormones affect glucose metabolism-related signaling pathway in skeletal muscles. We hypothesized that locally synthesized DHT from testosterone and/or DHEA activates glucose transporter-4 (GLUT-4)-regulating pathway in skeletal muscles. The aim of the present study was to clarify whether DHT is synthesized from testosterone and/or DHEA in cultured skeletal muscle cells and whether these hormones affect the GLUT-4-related signaling pathway in skeletal muscles. In the present study, the expression of 5alpha-reductase mRNA was detected in rat cultured skeletal muscle cells, and the addition of testosterone or DHEA increased intramuscular DHT concentrations. Addition of testosterone or DHEA increased GLUT-4 protein expression and its translocation. Furthermore, Akt and protein kinase C-zeta/lambda (PKC-zeta/lambda) phosphorylations, which are critical in GLUT-4-regulated signaling pathways, were enhanced by testosterone or DHEA addition. Testosterone- and DHEA-induced increases in both GLUT-4 expression and Akt and PKC-zeta/lambda phosphorylations were blocked by a DHT inhibitor. Finally, the activities of phosphofructokinase and hexokinase, main glycolytic enzymes, were enhanced by testosterone or DHEA addition. These findings suggest that skeletal muscle is capable of synthesizing DHT from testosterone, and that DHT activates the glucose metabolism-related signaling pathway in skeletal muscle cells.

Effect of 12 weeks of moderate–intensity resistance training on arterial stiffness: a randomised controlled trial in women aged 32–59 years

Background: Resistance training has been increasingly incorporated into the overall exercise programme because of its effect on muscle strength, functional capacity and osteoporosis. High-intensity resistance training increases arterial stiffness. However, the effect of moderate-intensity resistance training on arterial stiffness is unknown. Objective: To determine whether 12 weeks of moderate-intensity resistance training increases arterial stiffness in middle-aged women. Methods: 35 middle-aged women (age range 32 to 59 years) volunteered to participate. The subjects were randomly assigned to one of three groups: resistance training (RT) group, aerobic exercise training (AET) group or control group. The RT and AET groups performed 12 weeks of moderate-intensity resistance training or aerobic exercise training (two days/week). Results: In the RT group, one-repetition maximum strength significantly increased after the intervention. Interestingly, aortic (carotid–femoral) pulse wave velocity (PWV; an index of arterial stiffness), and peripheral (femoral–ankle) PWV did not change with moderate-intensity resistance training. In contrast, in the AET group, carotid–femoral PWV significantly decreased after the intervention. Resistance training and aerobic exercise training did not affect blood pressure. Conclusions: This study found that moderate-intensity resistance training did not increase arterial stiffness in middle-aged women, which may have great importance for health promotion with resistance training.

Effect of weight reduction with dietary intervention on arterial distensibility and endothelial function in obese men

Obesity and reduction in central arterial distensibility, respectively, have been identified as powerful and independent risk factors for cardiovascular disease. However, the effect of weight reduction on central arterial function in obese subjects has not yet been clarified. We investigated whether low-calorie diet-induced weight reduction affects central arterial distensibility and endothelial function in middle-aged obese men. Twelve obese men (age: 45+2 yrs, BMI: 30+1 kg/m 2) completed a 12-week dietary intervention. Caloric restriction induced significantly weight loss and decrease in BMI. After the program, carotid arterial compliance significantly increased and b-stiffness index and aortic pulse-wave velocity remarkably decreased. Concentrations of plasma endothelin-1 (ET-1) significantly decreased and plasma nitric oxide (NO) markedly increased after the program. Weight reduction by low-calorie diet in obese men increases central arterial distensibility, which may contribute to the improvement in endothelial function, as noted by a decrease in ET-1 and an increase in NO.

Effects of leg resistance training on arterial function in older men

Background: Little information is available on the effect of strength training on vascular function, particularly in older people. Objective: To determine the effect of resistance training on arterial stiffness and endothelial function in older adults. Method: Eleven healthy men (mean (SEM) age 64 (1) years) performed 12 weeks of resistance training involving knee flexion and extension (three sets a day, two days a week). Results: Resistance training increased maximal muscle power by 16% (p<0.0001). Arterial stiffness as assessed by aortic pulse wave velocity did not change with resistance training. Plasma concentration of nitric oxide (NO), measured as its stable end product (nitrite/nitrate), had increased (p<0.05) after resistance training (61.2 (10.4) v 39.6 (3.2) μmol/l). There was no change in plasma concentration of endothelin-1. Conclusion: The results suggest that short term resistance training may increase NO production without stiffening central arteries in healthy older men.

Comparison of epicardial, abdominal and regional fat compartments in response to weight loss

BACKGROUND AND AIMS Echocardiographic measurement of epicardial fat (EF) seems to be a reliable and diagnostic marker of visceral adipose tissue (VAT). However, the weight loss-induced changes in EF have not been compared with those in VAT or the truncal depot. In this study, we aimed to compare the weight loss-induced changes in EF, VAT and other regional fat compartments in obese men. METHODS AND RESULTS In this study, 27 moderately obese men (age 45.8+/-1.7 years; body mass index 30.5+/-0.7 kg/m(2)) followed a daily low-calorie diet as part of a clinical 12-week weight loss interventional study. We evaluated the EF thickness by transthoracic echocardiography, assessed the abdominal fat tissues by computed tomography scans, and examined the regional and whole body fat compartments by dual X-ray absorptiometry. An average decrease of 26.8% in the initial calorie intake corresponded to post-program reductions of 17.2%, 11.0%, 16.6%, and 29.8% in EF thickness (P<0.001), body mass, percentage fat mass, and abdominal fat compartments, respectively. The percentage change in VAT in response to weight loss was twice as high as the substantial change in EF tissue (P<0.001). CONCLUSION The results of the study suggest that a low-calorie diet-induced weight loss decreases EF thickness. Moderate diet-induced weight loss alone may represent an effective nonpharmacological strategy for reducing EF, which is a unique, pathogenic fat depot and an emerging marker of VAT.

Additive beneficial effects of lactotripeptides and aerobic exercise on arterial compliance in postmenopausal women

Central arterial compliance plays an important role in the functional abilities of the vasculature. Two active tripeptides, valine-proline-proline and isoleucine-proline-proline, were isolated from sour milk and were referred to as lactotripeptides (LTP). Because LTP appears to act as an angiotensin-converting enzyme inhibitor, it is plausible to hypothesize that LTP improves arterial compliance. We determined the effects of LTP ingestion alone or in combination with regular aerobic exercise on arterial compliance. A total of 55 postmenopausal women (50-65 yr old) were randomly divided into four groups: placebo, LTP, exercise and placebo (Ex + placebo), or exercise and LTP (Ex + LTP). LTP or placebo was administered orally for 8 wk. The exercise groups completed an 8-wk moderate aerobic exercise intervention. There were no differences in baseline arterial compliance and most other key dependent variables among the groups. Carotid arterial compliance increased significantly in the LTP (0.93 + or - 0.07 vs. 0.99 + or - 0.08 mm(2)/mmHg x 10(-1)), Ex + placebo (0.92 + or - 0.04 vs. 1.00 + or - 0.05 mm(2)/mmHg x 10(-1)), and Ex + LTP groups (0.86 + or - 0.06 vs. 1.00 + or - 0.06 mm(2)/mmHg x 10(-1)), whereas no such changes were observed in the placebo control group (0.86 + or - 0.06 vs. 0.85 + or - 0.07 mm(2)/mmHg x 10(-1)). The magnitude of increases in carotid arterial compliance was significantly greater in the Ex + LTP group (19 + or - 4%) than in other groups. The improvements in arterial compliance with LTP were associated with the corresponding reductions in arterial blood pressure and plasma angiotensin II concentrations. We concluded that LTP ingestion improves carotid arterial compliance and that the combination of LTP ingestion and regular exercise is additive and synergistic in improving arterial compliance in postmenopausal women.

Curcumin ingestion and exercise training improve vascular endothelial function in postmenopausal women.

Vascular endothelial function is declines with aging and is associated with an increased risk of cardiovascular disease. Lifestyle modification, particularly aerobic exercise and dietary adjustment, has a favorable effect on vascular aging. Curcumin is a major component of turmeric with known anti-inflammatory and anti-oxidative effects. We investigated the effects of curcumin ingestion and aerobic exercise training on flow-mediated dilation as an indicator endothelial function in postmenopausal women. A total of 32 postmenopausal women were assigned to 3 groups: control, exercise, and curcumin groups. The curcumin group ingested curcumin orally for 8 weeks. The exercise group underwent moderate aerobic exercise training for 8 weeks. Before and after each intervention, flow-mediated dilation was measured. No difference in baseline flow-mediated dilation or other key dependent variables were detected among the groups. Flow-mediated dilation increased significantly and equally in the curcumin and exercise groups, whereas no changes were observed in the control group. Our results indicated that curcumin ingestion and aerobic exercise training can increase flow-mediated dilation in postmenopausal women, suggesting that both can potentially improve the age-related decline in endothelial function.

Effect of Habitual Aerobic Exercise on Body Weight and Arterial Function in Overweight and Obese Men

The effect of habitual exercise on vascular function, including central arterial distensibility and endothelial function, in obese subjects has not yet been clarified. We investigated whether aerobic exercise training affects central arterial distensibility and endothelial function in middle-age overweight and obese men. A total of 21 overweight and obese men (age 50 +/- 2 years, body mass index 30 +/- 1 kg/m(2)) completed a 12-week aerobic exercise intervention. Aerobic exercise training significantly reduced their body weight and resulted in a significant decrease in body mass index. After the weight-reduction exercise program, carotid arterial compliance (determined by simultaneous B-mode ultrasonography and arterial applanation tonometry on the common carotid artery) significantly increased; and the beta-stiffness index, an index of arterial compliance adjusted for distending pressure, significantly decreased. The concentrations of plasma endothelin-1, a potent vasoconstrictor peptide produced by vascular endothelial cells, significantly decreased and plasma nitric oxide (measured as the stable end product [nitrite/nitrate]), a potent vasodilator produced by vascular endothelial cells, significantly increased after the weight-reduction exercise program. In conclusion, weight reduction by aerobic exercise training in overweight and obese men increased the central arterial distensibility. This increase might contribute to the improvement in endothelial function, as assessed by a decrease in endothelin-1 and an increase in nitric oxide, after exercise training-induced weight loss.

Involvement of endothelin-1 in habitual exercise-induced increase in arterial compliance.

Aim:  Habitual aerobic exercise results in a significant increase in central arterial compliance. Endothelin‐1 (ET‐1) is a potent endothelium‐derived vasoconstrictor peptide and could play a role in mediating the habitual aerobic exercise‐induced increase in central arterial compliance. The aim of the present study was to examine whether ET‐1 is involved in the mechanisms underlying the increase in central arterial compliance with aerobic exercise training.

Additive beneficial effects of lactotripeptides intake with regular exercise on endothelium-dependent dilatation in postmenopausal women.

BACKGROUND Peripheral conduit artery endothelium-dependent dilatation decreases with aging in humans. Lactotripeptides (LTPs) and regular exercise can improve endothelium-dependent dilatation, but combining these lifestyle modifications may be more effective than either treatment alone. We conducted a randomized, place-controlled trial with four different intervention arms. METHODS A total of 43 postmenopausal women (50-65 years old) were randomly divided into placebo, LTP, exercise and placebo (Ex+placebo), or exercise and LTP (Ex+LTP) groups. LTP or placebo was administered orally for 8 weeks. The exercise groups completed an 8-week moderate aerobic exercise (walking or cycling) intervention. RESULTS There were no statistically significant differences in baseline flow-mediated dilatation (FMD) and most other key dependent variables among the groups. FMD significantly increased in the LTP, Ex+placebo, and Ex+LTP groups whereas no such changes were observed in the placebo control group. The magnitude of increases in FMD was significantly greater in the Ex+LTP group than other intervention groups. CONCLUSION We concluded that LTP ingestion combined with regular aerobic exercise improves endothelium-dependent dilatation to a greater extent than monotherapy with either intervention alone in postmenopausal women.