The Q223R polymorphism in the leptin receptor associates with objectively measured light physical activity in free-living Japanese

AbstractPhysical activity (PA) is associated with reductions in the risk of all-cause mortality and in the prevalence of cardiovascular disease and stroke. Nevertheless, a large proportion of the general population may not be sufficiently active. PA level has been reported to be influenced by genetic factors, and we investigated whether Q223R polymorphism in the leptin receptor (LEPR) gene was associated with PA level. A total of 556 Japanese adults aged 24–65years old participated in this cross-sectional study. The duration and intensity of PA were objectively evaluated by triaxial accelerometry. Q223R polymorphism was determined by the TaqMan method. The distribution of Q223R polymorphism was: QQ 0.7%, QR 22.6%, and RR 76.6%. The relation between the LEPR genotype and PA level was analyzed by ANCOVA with age and sex as covariates in the Q dominant genetic model. There were significant differences between LEPR genotypes and the time spent in light PA or inactive time. The subjects with RR genotype showed significantly shorter time spent in light PA (RR genotype: 559.4±102.9min/day, QQ/QR genotype: 579.9±103.1min/day) and longer inactive time (RR genotype: 815.5±107.5min/day, QQ/QR genotype: 792.3±107.7min/day) than the subjects with QQ/QR genotype (P<0.05). There were no such differences in the time spent in moderate or vigorous PA. These results suggest that the variety of PA level, especially spontaneous PA in humans, is partly caused by diversity in the LEPR gene

DHEA administration and exercise training improves insulin resistance in obese rats

Background: Dehydroepiandrosterone (DHEA) is precursor of sex steroid hormone. We demonstrated that acute DHEA injection to type 1 diabetes model rats induced improvement of hyperglycemia. However, the effect of the combination of DHEA administration and exercise training on insulin resistance is still unclear. This study was undertaken to determine whether 6-weeks of DHEA administration and/or exercise training improve insulin resistance in obese male rats. Methods: After 14 weeks of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of four groups: control, DHEA administration, exercise training, and a combination of DHEA administration and exercise training (n = 10 each group). Results: After 6-weeks of DHEA administration and/or exercise training, rats in the combination group weighed significantly less and had lower serum insulin levels than rats in the other groups. Moreover, the rats treated with DHEA alone or DHEA and exercise had significantly lower fasting glucose levels (combination, 84 ± 6.5 mg/dL; DHEA, 102 ± 9.5 mg/dL; control, 148 ± 10.5 mg/dL). In addition, insulin sensitivity check index showed significant improvements in the combination group (combination, 0.347 ± 0.11; exercise, 0.337 ± 0.16%; DHEA, 0.331 ± 0.14; control, 0.308 ± 0.12). Muscular DHEA and 5α-dihydrotestosterone (DHT) concentrations were significantly higher in the combination group, and closely correlated with the quantitative insulin-sensitivity check index (DHEA: r = 0.71, p < 0.01; DHT: r = 0.69, p < 0.01). Conclusion: These results showed that a combination of DHEA administration and exercise training effectively improved fasting blood glucose and insulin levels, and insulin sensitivity, which may reflect increased muscular DHEA and DHT concentrations

Arterial Stiffness, Physical Activity, and Atrial Natriuretic Peptide Gene Polymorphism in Older Subjects

An increase in arterial stiffness with advancing age is associated with several pathological states, includinghypertension and arteriosclerosis. Regular exercise improves the aging-induced increase in arterial stiffnessand has a protective effect against these diseases. However, not all individuals respond to exerciseto the same extent. Atrial natriuretic peptide (ANP) is involved in the regulation of basal blood pressure,blood flow, and vascular tone. The present study was designed to clarify whether gene polymorphisms inANP-related genes affect exercise-induced improvements in arterial stiffness. We performed a cross-sectionalstudy of 291 healthy middle-aged and older Japanese subjects (63±1 years), examining the relationshipbetween daily physical activity–induced improvements in arterial stiffness, estimated by brachial-anklearterial pulse wave velocity (baPWV), and the gene polymorphisms of valine32methionine (V32M: 664G>A)in exon 1 of ANP and asparagine521aspartic acid (N521D: 1780A>G) in exon 8 of the ANP clearance receptor(NPR-C). The baseline baPWV was significantly lower in the active group, but no differences were seen inblood pressure. Active subjects with the ANP-VV genotype had significantly lower baPWV and higherplasma ANP levels compared with inactive subjects, but there were no variations related to the VM+MMgenotype. Additionally, baPWV and plasma ANP levels were negatively correlated in ANP-VV genotypesubjects, but were not correlated in VM+MM individuals. Our results suggest that ANP polymorphismin older Japanese subjects may affect the cardiovascular response to regular exercise

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 17β- and 3β-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

Mechanisms of exercise-induced improvements in the contractile apparatus of the mammalian myocardium

One of the main outcomes of aerobic endurance exercise training is the improved maximal oxygen uptake, and this is pivotal to the improved work capacity that follows the exercise training. Improved maximal oxygen uptake in turn is at least partly achieved because exercise training increases the ability of the myocardium to produce a greater cardiac output. In healthy subjects, this has been demonstrated repeatedly over many decades. It has recently emerged that this scenario may also be true under conditions of an initial myocardial dysfunction. For instance, myocardial improvements may still be observed after exercise training in post-myocardial infarction heart failure. In both health and disease, it is the changes that occur in the individual cardiomyocytes with respect to their ability to contract that by and large drive the exercise training-induced adaptation to the heart. Here, we review the evidence and the mechanisms by which exercise training induces beneficial changes in the mammalian myocardium, as obtained by means of experimental and clinical studies, and argue that these changes ultimately alter the function of the whole heart and contribute to the changes in whole-body function

Salivary Secretory Immunoglobulin a secretion increases after 4-weeks ingestion of chlorella-derived multicomponent supplement in humans: a randomized cross over study

<p>Abstract</p> <p>Background</p> <p>Chlorella, a unicellular green alga that grows in fresh water, contains high levels of proteins, vitamins, minerals, and dietary fibers. Some studies have reported favorable immune function-related effects on biological secretions such as blood and breast milk in humans who have ingested a chlorella-derived multicomponent supplement. However, the effects of chlorella-derived supplement on mucosal immune functions remain unclear. The purpose of this study was to investigate whether chlorella ingestion increases the salivary secretory immunoglobulin A (SIgA) secretion in humans using a blind, randomized, crossover study design.</p> <p>Methods</p> <p>Fifteen men took 30 placebo and 30 chlorella tablets per day for 4 weeks separated by a 12-week washout period. Before and after each trial, saliva samples were collected from a sterile cotton ball that was chewed after overnight fasting. Salivary SIgA concentrations were measured using ELISA.</p> <p>Results</p> <p>Compliance rates for placebo and chlorella ingestions were 97.0 ± 1.0% and 95.3 ± 1.6%, respectively. No difference was observed in salivary SIgA concentrations before and after placebo ingestion (<it>P </it>= 0.38). However, salivary SIgA concentrations were significantly elevated after chlorella ingestion compared to baseline (<it>P </it>< 0.01). No trial × period interaction was identified for the saliva flow rates. Although the SIgA secretion rate was not affected by placebo ingestion (<it>P </it>= 0.36), it significantly increased after 4-week chlorella ingestion than before intake (<it>P </it>< 0.01).</p> <p>Conclusions</p> <p>These results suggest 4-week ingestion of a chlorella-derived multicomponent supplement increases salivary SIgA secretion and possibly improves mucosal immune function in humans.</p

Deep RNA Sequencing Reveals Novel Cardiac Transcriptomic Signatures for Physiological and Pathological Hypertrophy

Although both physiological hypertrophy (PHH) and pathological hypertrophy (PAH) of the heart have similar morphological appearances, only PAH leads to fatal heart failure. In the present study, we used RNA sequencing (RNA-Seq) to determine the transcriptomic signatures for both PHH and PAH. Approximately 13–20 million reads were obtained for both models, among which PAH showed more differentially expressed genes (DEGs) (2,041) than PHH (245). The expression of 417 genes was barely detectable in the normal heart but was suddenly activated in PAH. Among them, Foxm1 and Plk1 are of particular interest, since Ingenuity Pathway Analysis (IPA) using DEGs and upstream motif analysis showed that they are essential hub proteins that regulate the expression of downstream proteins associated with PAH. Meanwhile, 52 genes related to collagen, chemokines, and actin showed opposite expression patterns between PHH and PAH. MAZ-binding motifs were enriched in the upstream region of the participating genes. Alternative splicing (AS) of exon variants was also examined using RNA-Seq data for PAH and PHH. We found 317 and 196 exon inclusions and exon exclusions, respectively, for PAH, and 242 and 172 exon inclusions and exclusions, respectively for PHH. The AS pattern was mostly related to gains or losses of domains, changes in activity, and localization of the encoded proteins. The splicing variants of 8 genes (i.e., Fhl1, Rcan1, Ndrg2, Synpo, Ttll1, Cxxc5, Egfl7, and Tmpo) were experimentally confirmed. Multilateral pathway analysis showed that the patterns of quantitative (DEG) and qualitative (AS) changes differ depending on the type of pathway in PAH and PHH. One of the most significant changes in PHH is the severe downregulation of autoimmune pathways accompanied by significant AS. These findings revealed the unique transcriptomic signatures of PAH and PHH and also provided a more comprehensive understanding at both the quantitative and qualitative levels