Effects of lactotripeptide ingestion and physical activity intervention on the fatigue status of middle-aged and older adults: a randomized controlled trial.

This randomized controlled trial aimed to investigate the effects of eight weeks of lactotripeptide (LTP) ingestion, physical activity (PA) intervention, and combined intervention on the fatigue status of middle-aged and older adults. A total of 78 middle-aged and older adults (63 ± 8 years of age) were randomly assigned to four groups: placebo, LTP, placebo with PA intervention (placebo + PA), and LTP with PA intervention (LTP + PA). All participants ingested the placebo or LTP tablets daily (three tablets/day). The placebo + PA and LTP + PA groups participated in a weekly supervised exercise class and were instructed to increase their moderate- to vigorous-intensity PA at home. The visual analog scale, Brief Fatigue Inventory, Profile of Mood States second edition (POMS2), and Beck Depression Inventory second edition (BDI-II) were administered before and after the intervention. No significant interactions or main effects were observed between LTP ingestion and PA intervention on any of the fatigue scales. The main-effect analyses revealed that the PA intervention improved the total mood disturbance score of the POMS2 (F = 5.22, P = 0.03) and BDI-II score (F = 4.81, P = 0.03). After the post hoc paired comparisons, the total mood disturbance and BDI-II scores improved more with the combined intervention than with the PA intervention alone (percentage difference between the effect of combined intervention and PA intervention alone was 3.7% for total mood disturbance score and 13.7% for BDI-II score). The present study suggests that eight weeks of LTP ingestion and PA intervention did not have a significant effect on fatigue status. However, the PA intervention improved mood status and depressive symptoms, and these effects were enhanced by LTP ingestion.

Genetic polymorphisms related to muscular strength and flexibility are associated with artistic gymnastic performance in the Japanese population.

This study aimed to examine how genetic polymorphisms related to muscular strength and flexibility influence artistic gymnastic performance in an attempt to identify a novel polymorphism associated with flexibility. In study 1, the passive straight-leg-raise (PSLR) score and aromatase gene CYP19A1 rs936306 polymorphism, a key enzyme for estrogen biosynthesis, were assessed in 278 individuals. In study 2, athletes (281 gymnasts and 1908 other athletes) were asked about their competition level, and gymnasts were assessed using the difficulty score (D-score) for each event. Muscular strength- (ACTN3 R577X rs1815739 and ACE I/D rs4341) and flexibility-related (ESR1 rs2234693 T/C and CYP19A1 rs936306 C/T) genetic polymorphisms were analyzed. In study 1, males with the CYP19A1 CT + TT genotype showed significantly higher PSLR scores than those with the CC genotype. In study 2, male gymnasts with the R allele of ACTN3 R577X showed a correlation with the floor, rings, vault, and total D-scores. In addition, male gymnasts with the C allele of ESR1 T/C and T allele of CYP19A1 C/T polymorphisms were correlated with the pommel horse, parallel bars, horizontal bar, and total D-scores. Furthermore, genotype scores of these three polymorphisms correlated with the total D-scores and competition levels in male gymnasts. In contrast, no such associations were observed in female gymnasts. Our findings suggest that muscular strength- and flexibility-related polymorphisms play important roles in achieving high performance in male artistic gymnastics by specifically influencing the performance of events that require muscular strength and flexibility, respectively.HighlightsEstrogen-related CYP19A1 polymorphism is a novel determinant of flexibility in males.Muscular strength- and flexibility-related polymorphisms play important roles in high performance in male artistic gymnastics.Genotypes of ACTN3 R577X, ESR1 rs2234693, and CYP19A1 rs936306 may contribute to training plan optimization and event selection in artistic gymnastics.

Replacing sedentary time for physical activity on bone density in patients with chronic kidney disease.

INTRODUCTION: This study aimed to examine the cross-sectional associations of sedentary time and physical activity time with bone density in patients with chronic kidney disease (CKD). The isotemporal substitution (IS) modeling was used to estimate the beneficial effects of behavioral changes (e.g., replacing sedentary time with physical activity time) on bone density in these patients. MATERIALS AND METHODS: A total of 92 patients with CKD (age: 65 ± 9 years; estimated glomerular filtration rate: 57 ± 22 mL/min/1.73 m2) were included in this cross-sectional study. The times spent in sedentary behavior (SB), light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were assessed using a triaxial accelerometer. Through quantitative ultrasound measurements, the stiffness index, as a measure of bone density, was calculated using the speed of sound and broadband ultrasound attenuation. RESULTS: In multivariate analyses, the stiffness index was beneficially associated with the MVPA time (ß = 0.748), but was not significantly associated with the SB and LPA times. The IS models showed that replacing 10 min/day of SB with the equivalent LPA time was not significantly associated with the stiffness index; however, replacing 10 min/day of SB with the equivalent MVPA time was beneficially associated with the stiffness index (ß = 0.804). CONCLUSION: These results suggest that a small increase in MVPA time (e.g., 10 min/day) may attenuate the decline in bone density in patients with CKD. Our findings may provide insight for the development of novel strategies for improving bone health in patients with CKD.

A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c.

Type 2 Diabetes (T2D) is an emerging public health problem in Asia. Although ethnic specific mtDNA polymorphisms have been shown to contribute to T2D risk, the functional effects of the mtDNA polymorphisms and the therapeutic potential of mitochondrial-derived peptides at the mtDNA polymorphisms are underexplored. Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n = 27,527, J-MICC, MEC, and TMM) show that males but not females with the C-allele exhibit a higher prevalence of T2D. In J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.

High Salt Diet Impacts the Risk of Sarcopenia Associated with Reduction of Skeletal Muscle Performance in the Japanese Population.

The World Health Organization has recommended 5 g/day as dietary reference intakes for salt. In Japan, the averages for men and women were 11.0 g/day and 9.3 g/day, respectively. Recently, it was reported that amounts of sodium accumulation in skeletal muscles of older people were significantly higher than those in younger people. The purpose of this study was to investigate whether the risk of sarcopenia with decreased muscle mass and strength was related to the amount of salt intake. In addition, we investigated its involvement with renalase. Four groups based on age and salt intake ("younger low-salt," "younger high-salt," "older low-salt," and "older high-salt") were compared. Stratifying by age category, body fat percentage significantly increased in high-salt groups in both younger and older people. Handgrip strength/body weight and chair rise tests of the older high-salt group showed significant reduction compared to the older low-salt group. However, there was no significant difference in renalase concentrations in plasma. The results suggest that high-salt intake may lead to fat accumulation and muscle weakness associated with sarcopenia. Therefore, efforts to reduce salt intake may prevent sarcopenia.

Sedentary behaviour, physical activity, and renal function in older adults: isotemporal substitution modelling.

BACKGROUND: Physical inactivity and sedentary behaviour (too much sitting) can contribute to renal dysfunction. However, the potential benefits of behavioural change (e.g. replacing sedentary behaviour with physical activity) on renal function are not well understood. We used isotemporal substitution to model potential impacts of behaviours on renal function by replacing time spent in one behaviour to another. METHODS: In 174 older Japanese adults (age, 50-83 years; females, 76%), the time spent in sedentary behaviour, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA) were assessed using an uniaxial accelerometer. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) from serum creatinine and cystatin C levels. RESULTS: In univariate analyses, eGFR was significantly, albeit weakly, correlated with time spent in sedentary behaviour (rs = - 0.229), LPA (rs = 0.265), and MVPA (rs = 0.353). In the isotemporal substitution models, replacement of 30 min/day of sedentary behaviour with an equivalent LPA time was not significantly associated with eGFR (ß = 2.26, p = 0.112); however, replacement with an equivalent time of MVPA was beneficially associated with eGFR (ß = 5.49, p < 0.05). CONCLUSIONS: These cross-sectional findings suggest that sedentary behaviour (detrimentally) and physical activity (beneficially) may affect renal function and that replacing sedentary behaviour with MVPA may benefit renal health in older adults.

Increased fibroblast growth factor-21 in chronic kidney disease is a trade-off between survival benefit and blood pressure dysregulation.

Circulating levels of fibroblast growth factor-21 (FGF21) start increasing in patients with chronic kidney disease (CKD) since early stages during the cause of disease progression. FGF21 is a liver-derived hormone that induces responses to stress through acting on hypothalamus to activate the sympathetic nervous system and the hypothalamus-pituitary-adrenal endocrine axis. However, roles that FGF21 plays in pathophysiology of CKD remains elusive. Here we show in mice that FGF21 is required to survive CKD but responsible for blood pressure dysregulation. When introduced with CKD, Fgf21-/- mice died earlier than wild-type mice. Paradoxically, these Fgf21-/- CKD mice escaped several complications observed in wild-type mice, including augmentation of blood pressure elevating response and activation of the sympathetic nervous system during physical activity and increase in serum noradrenalin and corticosterone levels. Supplementation of FGF21 by administration of an FGF21-expressing adeno-associated virus vector recapitulated these complications in wild-type mice and restored the survival period in Fgf21-/- CKD mice. In CKD patients, high serum FGF21 levels are independently associated with decreased baroreceptor sensitivity. Thus, increased FGF21 in CKD can be viewed as a survival response at the sacrifice of blood pressure homeostasis.

Lactotripeptide ingestion increases cerebral blood flow velocity in middle-aged and older adults.

The age-related decrease in cerebral blood flow velocity increases the risk of cerebrovascular disease. Milk protein-derived bioactive peptides, e.g., lactotripeptide (LTP), have been shown to inhibit angiotensin converting enzyme activities and increase vasodilator production. We hypothesized that LTP ingestion increases cerebral blood flow velocity in middle-aged and older adults. In a randomized, placebo-controlled, double-blind design, 15 healthy middle-aged and older adults were assigned to either a LTP group or a placebo group. The subjects ingested LTP or placebo orally for 8 weeks. Before and after intervention, middle cerebral blood flow velocity was measured using transcranial Doppler ultrasonography. The baseline middle cerebral blood flow velocity and most other key dependent variables did not differ between the groups. LTP ingestion significantly increased middle cerebral blood flow velocity, but there was no such improvement in the placebo groups. We concluded that 8 weeks of LTP ingestion increased middle cerebral blood flow velocity in middle-aged and older adults.

Which cytokine is the most related to weight loss-induced decrease in arterial stiffness in overweight and obese men?

Obesity and increased arterial stiffness are risk factors for cardiovascular disease. A well-known characteristic of obesity is the chronic low-grade inflammatory state, and it causes elevation of arterial stiffness. Weight-loss reduces arterial stiffness and inflammatory level in obese individuals. However, it is unclear which inflammatory factor is most related to weight loss-induce decreases in arterial stiffness in overweight and obese men. Thus, the aim of this study was to determine which circulating cytokine level has the most effect on decreasing arterial stiffness after lifestyle modification. Twenty overweight and obese men completed a 12-week period of lifestyle modifications (combination of aerobic exercise training and dietary modification). We measured brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness, and circulating cytokine levels using comprehensive analysis. After the 12-week lifestyle modifications, body mass was markedly decreased. Also, baPWV and the levels of several circulating cytokines significantly decreased after the lifestyle modifications. We observed a positive correlation between changes in baPWV and circulating interleukin-6 (IL-6) levels. Furthermore, multiple liner regression analysis revealed that change in baPWV was significantly associated with that in IL-6 levels after consideration of changes in systolic blood pressure and body mass index. These results suggest that for overweight and obese men, a 12-week period of lifestyle modifications-induced a decrease in circulating cytokine levels (especially IL-6 levels), leads to decreased baPWV.

Effect of Chlorella-derived multicomponent supplementation on maximal oxygen uptake and serum vitamin B2 concentration in young men.

Chlorella is a unicellular green alga that contains high levels of proteins, vitamins and minerals. The present study investigated the effects of a 4-week Chlorella-derived multicomponent supplementation on maximal oxygen uptake and circulating vitamin B2 levels in healthy men. Thirty-four participants were randomly divided into two groups: placebo or Chlorella. Prior to the intervention, we observed that the intake of several minerals and soluble vitamins did not satisfy the nutrient requirements of either group by assessing the frequency of daily food intake. There was a significant negative relationship between the pre-intervention maximal oxygen uptake and serum vitamin B2 concentrations in all subjects (r = -0.372). Maximal oxygen uptake significantly increased after Chlorella supplementation (before vs after, 42.1 ± 1.5 vs 44.9 ± 1.6 ml/kg/min), while serum vitamin B2 concentrations did not (14.6 ± 0.9 vs 14.0 ± 0.9 µg/L). In conclusion, Chlorella-derived multicomponent supplementation increases maximal oxygen uptake in individuals with an insufficient micronutrient status, although there was no association between the increase in aerobic capacity and serum levels of vitamin B2.

Deficiency of the hepatokine selenoprotein P increases responsiveness to exercise in mice through upregulation of reactive oxygen species and AMP-activated protein kinase in muscle.

Exercise has numerous health-promoting effects in humans; however, individual responsiveness to exercise with regard to endurance or metabolic health differs markedly. This 'exercise resistance' is considered to be congenital, with no evident acquired causative factors. Here we show that the anti-oxidative hepatokine selenoprotein P (SeP) causes exercise resistance through its muscle receptor low-density lipoprotein receptor-related protein 1 (LRP1). SeP-deficient mice showed a 'super-endurance' phenotype after exercise training, as well as enhanced reactive oxygen species (ROS) production, AMP-activated protein kinase (AMPK) phosphorylation and peroxisome proliferative activated receptor γ coactivator (Ppargc)-1α (also known as PGC-1α; encoded by Ppargc1a) expression in skeletal muscle. Supplementation with the anti-oxidant N-acetylcysteine (NAC) reduced ROS production and the endurance capacity in SeP-deficient mice. SeP treatment impaired hydrogen-peroxide-induced adaptations through LRP1 in cultured myotubes and suppressed exercise-induced AMPK phosphorylation and Ppargc1a gene expression in mouse skeletal muscle-effects which were blunted in mice with a muscle-specific LRP1 deficiency. Furthermore, we found that increased amounts of circulating SeP predicted the ineffectiveness of training on endurance capacity in humans. Our study suggests that inhibitors of the SeP-LRP1 axis may function as exercise-enhancing drugs to treat diseases associated with a sedentary lifestyle.

Changes in salivary flow rate following Chlorella-derived multicomponent supplementation.

Decreases in saliva secretion compromise food mastication and swallowing, reduce mucosal immune function, and increase the risk for oral diseases like dental caries. Chlorella is a green alga that contains a variety of nutrients including amino acids, vitamins, and minerals. In our previous study, Chlorella-derived multicomponent supplementation did not affect salivary flow rates in healthy young individuals, but Chlorella-derived supplementation attenuated a decrease in saliva secretion that was observed during a kendo training camp. Hence, we hypothesized that Chlorella-derived supplementation increases saliva secretion in individuals with lower rates of saliva flow. Sixty-four subjects took Chlorella-derived tablets for four weeks. Before and after supplementation, saliva samples were collected by chewing cotton. In the complete study group, there was no difference in saliva production before and after supplementation (1.91 ± 0.11 ml/min before vs 2.01 ± 0.12 ml/min after). Analysis of subgroups based on saliva production before supplementation found an increase in saliva secretion in the lower saliva flow group (1.18 ± 0.06 vs 1.38 ± 0.08 ml/min), but no change in the higher saliva flow group (2.63 ± 0.11 vs 2.64 ± 0.15 ml/min). These results suggest that Chlorella-derived multicomponent supplementation increases saliva production in individuals with lower levels of saliva secretion.

Increased physical activity has a greater effect than reduced energy intake on lifestyle modification-induced increases in testosterone.

Obesity has reached epidemic proportions worldwide. Obesity results in reduced serum testosterone levels, which causes many disorders in men. Lifestyle modifications (increased physical activity and calorie restriction) can increase serum testosterone levels. However, it is unknown whether increased physical activity or calorie restriction during lifestyle modifications has a greater effects on serum testosterone levels. Forty-one overweight and obese men completed a 12-week lifestyle modification program (aerobic exercise training and calorie restriction). We measured serum testosterone levels, the number of steps, and the total energy intake. We divided participants into two groups based on the median change in the number of steps (high or low physical activities) or that in calorie restriction (high or low calorie restrictions). After the program, serum testosterone levels were significantly increased. Serum testosterone levels in the high physical activity group were significantly higher than those in the low activity group. This effect was not observed between the groups based on calorie restriction levels. We found a significant positive correlation between the changes in serum testosterone levels and the number of steps. Our results suggested that an increase in physical activity greatly affected the increased serum testosterone levels in overweight and obese men during lifestyle modification.

Attenuation of indirect markers of eccentric exercise-induced muscle damage by curcumin.

PURPOSE: Polyphenolic curcumin is known to have potent anti-inflammatory effects; thus the present study investigated the hypothesis that curcumin ingestion would attenuate muscle damage after eccentric exercise. METHODS: Fourteen untrained young men (24 ± 1 years) performed 50 maximal isokinetic (120°/s) eccentric contractions of the elbow flexors of one arm on an isokinetic dynamometer and the same exercise with the other arm 4 weeks later. They took 150 mg of curcumin (theracurmin) or placebo (starch) orally before and 12 h after each eccentric exercise bout in a randomised, crossover design. Maximal voluntary contraction (MVC) torque of the elbow flexors, range of motion of the elbow joint, upper-arm circumference, muscle soreness, serum creatine kinase (CK) activity, and plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration were measured before, immediately after, and 24, 48, 72 and 96 h after each eccentric exercise. Changes in these variables over time were compared between curcumin and placebo conditions by two-way repeated measures ANOVA. RESULTS: MVC torque decreased smaller and recovered faster (e.g., 4 days post-exercise: -31 ± 13 % vs. -15 ± 15 %), and peak serum CK activity was smaller (peak: 7684 ± 8959 IU/L vs. 3398 ± 3562 IU/L) for curcumin than placebo condition (P < 0.05). However, no significant differences between conditions were evident for other variables, and no significant changes in IL-6 and TNF-α were evident after exercise. CONCLUSION: It is concluded that theracurmin ingestion attenuates some aspects of muscle damage such as MVC loss and CK activity increase.

Lifestyle modification increases serum testosterone level and decrease central blood pressure in overweight and obese men.

Obesity has reached global epidemic proportions and is associated with multiple comorbidities, including cardiovascular disease. A novel predictor of cardiovascular disease is elevated central systolic blood pressure. In fact, lifestyle modifications have been shown to decrease the central systolic blood pressure in overweight and obese men. The mechanism underlying these changes has yet to be fully elucidated. Interestingly, testosterone has been found to have cardioprotective effects. Moreover, serum testosterone levels are lower in obese men than in normal weight men. However, it is still unclear whether testosterone participates in the decrease of central blood pressure in overweight and obese men following lifestyle modifications. So, the purpose of the present study was to investigate the effect of testosterone on central systolic blood pressure in overweight and obese men before and after the 12-week lifestyle modification program. Forty-four overweight and obese men completed a 12-week lifestyle modification program (aerobic exercise training and dietary modifications). For all participants, central systolic blood pressure and serum testosterone levels were measured before and after the program. After the program, central systolic blood pressure was significantly decreased while serum total testosterone levels were significantly increased in overweight and obese men. Moreover, we also found a significant negative relationship between the change in serum testosterone levels and that in central systolic blood pressure. The present study suggests that increased serum testosterone levels likely contribute to a decrease in central blood pressure in overweight and obese men.

Lifestyle modification decreases arterial stiffness in overweight and obese men: dietary modification vs. exercise training.

Obesity and increased arterial stiffness are independent risk factors for cardiovascular disease. Arterial stiffness is increased in obese individuals than in age-matched nonobese individuals. We demonstrated that dietary modification and exercise training are effective in reducing arterial stiffness in obese persons. However, the differences in the effect on arterial stiffness between dietary modification and exercise training are unknown. The purpose of the current study was to compare the effect of dietary modification and aerobic exercise training on arterial stiffness and endothelial function in overweight and obese persons. Forty-five overweight and obese men (48 ± 1 year) completed either a dietary modification (well-balanced nutrient, 1680 kcal/day) or an exercise-training program (walking, 40-60 min/day, 3 days/week) for 12 weeks. Before and after the intervention, all participants underwent anthropometric measurements. Arterial stiffness was measured based on carotid arterial compliance, brachial-ankle pulse wave velocity (baPWV), and endothelial function was determined by circulating level of endothelin-1 (ET-1) and nitric oxide metabolite (nitrites/nitrate as metabolite: NOx). Body mass and waist circumference significantly decreased after both intervention programs. Weight loss was greater after dietary modification than after exercise training (-10.1 ± 0.6 kg vs. -3.6 ± 0.5 kg, p < .01). Although arterial stiffness and the plasma levels of ET-1 and NOx were improved after dietary modification or exercise training, there were no differences in those improvements between the 2 types of interventions. Exercise training improves arterial function in obese men without as much weight loss as after dietary modification.

Effects of selective endothelin (ET)-A receptor antagonist versus dual ET-A/B receptor antagonist on hearts of streptozotocin-treated diabetic rats.

AIMS: The aim was to study the differences in the effectiveness of two types of endothelin (ET) receptor antagonists (selective ET-A or dual ET-A/B antagonists) on the hearts of streptozotocin (STZ)-induced diabetic rats (type I diabetes) at functional and biochemical/molecular levels. MAIN METHODS: Citrate saline (vehicle) or STZ was injected into rats. The ET-A/B dual receptor antagonist (SB209670, 1mg/kg/day) and the ET-A receptor antagonist (TA-0201, 1mg/kg/day) were then administered to these rats. One week after injection, the animals were separated into those receiving SB209670, TA-0201 or vehicle by 4-week osmotic mini-pump. KEY FINDINGS: The VEGF level and percent fractional shortening in the diabetic heart were significantly decreased compared to the non-diabetic heart, whereas SB209670 and TA-0201 treatments greatly and comparably prevented this decrease. SB209670 treatment was more effective in reversing decreased expressions of KDR and phosphorylated AKT, downstream of VEGF angiogenic signaling, than TA-0201 treatment. The eNOS levels in hearts were significantly higher in diabetic rats than in healthy rats, and this increase was significantly reduced by TA-0210 but not by SB209670 treatment. SIGNIFICANCE: Improvement of KDR mRNA and pAKT levels by SB209670 but not TA-0201 suggests that dual ET-A/-B blockade may be effective in improving intracellular systems of these components in the diabetic rat heart. However, the present study also showed that TA-0201 or SB209670 improved percent fractional shortening and VEGF levels of the diabetic hearts to a similar extent, suggesting that ET-A blockade and dual ET-A/-B blockade are similarly effective in improving cardiac dysfunction in the diabetic rats.

Fish oil constituent eicosapentaenoic acid inhibits endothelin-induced cardiomyocyte hypertrophy via PPAR-α.

AIMS: A growing body of evidence shows the cardiovascular benefits of fish oil ingredients, including eicosapentaenoic acid (EPA), in humans and experimental animals. However, the effects of EPA on endothelin (ET)-1-induced cardiomyocyte hypertrophy and the involved signaling cascade are largely unknown. A previous study has demonstrated that peroxisomal proliferator-activated receptor (PPAR)-α ligand (fenofibrate) prevents ET-1-induced cardiomyocyte hypertrophy. Although EPA is a ligand of PPAR-α, to date, no study has examined a relationship between EPA and PPAR-α in cardiomyocyte hypertrophy. Here, we investigated whether EPA can block ET-1-induced cardiomyocyte hypertrophy and the possible underlying mechanisms. MAIN METHODS: At day 4 of culture, neonatal rat cardiomyocytes were divided into four groups: control, control cells treated with EPA (10 µM), ET-1 (0.1 nM) administered only and EPA-pre-treated ET-1 administered groups. Also, the cardiomyocytes were treated with PPAR-α siRNA in order to elucidate the mechanisms that may underlie suppression of hypertrophy via the EPA-PPAR system. KEY FINDINGS: Following ET-1 treatment, 2.12- and 1.92-fold increases in surface area and total protein synthesis rate in cardiomyocytes, respectively, were observed and these changes were greatly blocked by EPA pre-treatment. Further, the expression of PPAR-α increased in EPA-treated groups. PPAR-PPRE binding activity was suppressed in ET-1 administered cardiomyocyte and this suppression was improved by EPA treatment. Lastly, pre-treatment of cardiomyocytes with PPAR-α siRNA prior to EPA treatment attenuated the suppressing effects of EPA on cardiomyocyte hypertrophy. SIGNIFICANCE: In conclusion, the present study shows that EPA attenuates ET-1 induced cardiomyocyte hypertrophy by up regulating levels of PPAR-α pathway.

Effect of endurance exercise training and curcumin intake on central arterial hemodynamics in postmenopausal women: pilot study.

BACKGROUND: Lifestyle modification (i.e., regular physical activity and diet) is effective in preventing the age-related increase in cardiovascular disease risks. Potential therapeutic effects of curcumin (diferuloylmethane) have been confirmed on various diseases, including cancer and Alzheimer's disease, but the effects of curcumin have not been tested on central arterial hemodynamics. The aim of this pilot study was to test the hypothesis that the regular endurance exercise combined with daily curcumin ingestion lowers the age-related increase in left ventricular (LV) afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women using a randomized, double-blind, placebo-controlled, parallel manner. METHODS: Forty-five women were randomly assigned to four interventions: "placebo ingestion" (n = 11), "curcumin ingestion" (n = 11), "exercise training with placebo ingestion" (n = 11), or "exercise training with curcumin ingestion" (n = 12). Curcumin or placebo pills (150 mg/day) were administered for 8 weeks. Aortic blood pressure (BP) and augmentation index (AIx), an index of LV afterload, were evaluated by pulse wave analysis from tonometrically measured radial arterial pressure waveforms. RESULTS: There were no significant differences in baseline hemodynamic variables among four groups. After the interventions, brachial systolic BP (SBP) significantly decreased in both exercise-trained groups (P < 0.05 for both), whereas aortic SBP significantly decreased only in the combined-treatment (e.g., exercise and curcumin) group (P < 0.05). Heart rate (HR) corrected aortic AIx significantly decreases only in the combined-treatment group. CONCLUSIONS: These findings suggest that regular endurance exercise combined with daily curcumin ingestion may reduce LV afterload to a greater extent than monotherapy with either intervention alone in postmenopausal women.

DHEA administration activates local bioactive androgen metabolism in cancellous site of tibia of ovariectomized rats.

It is not known whether local androgen metabolism is involved in the mechanisms underlying the dehydroepiandrosterone (DHEA) administration-induced improvement of bone mineral density (BMD) in an estrogen-deficiency state. The aim of the present study was to clarify whether DHEA administration would improve local androgen metabolism and BMD in cancellous site of tibia of ovariectomized (OVX) rats. Twenty-two female rats, 6 weeks old, were randomized into three groups: sham-operated rats, OVX control rats, and OVX rats that received DHEA treatment. DHEA was administered intraperitoneally at 20 mg/kg body weight for 8 weeks. The concentrations of free testosterone and dihydrotestosterone (DHT) in cancellous site of tibia did not change as a result of ovariectomy, while the DHT concentration increased following DHEA administration. We revealed that DHEA administration improved the reduction of 17ß- and 3ß-hydroxysteroid dehydrogenases and clearly reversed the reduction of 5α-reductase types 1 and 2 and androgen receptor in the cancellous site of tibia of OVX rats. DHEA administration suppressed estrogen deficiency relative to the decrease in the cancellous BMD, which was positively associated with local DHT concentration. These findings indicate that DHEA administration enhances local bioactive androgen metabolism in the cancellous tibia of young OVX rats, suggesting that local DHT may play a part in the DHEA administration-induced improvement of cancellous BMD.