Search

Olfactory dysfunction is associated with poor physical performance in older adults. However, it remains unknown whether the ability to identify particular olfactory clusters and/or odors is associated with physical performance in physically independent community-dwelling older adults.This cross-sectional study included 130 community-dwelling older adults (70.1 ± 5.5 years). The Odor Stick Identification Test for Japanese people, consisting of 12 odors in four clusters (wood, grass, herb; sweet; spices; foul-smelling), was used to examine olfaction. Participants also completed physical performance tests (one leg standing with open eyes; aerobic capacity; lower muscle function: five-times chair stand [CS] and vertical jump; mobility: star walking and timed up and go [TUG]) and cognitive function tests.Worse overall olfaction was not significantly associated with any physical performance measure. Worse performance for identifying sweet odors and an inability to identify some specific odors (menthol and rose) were associated with worse mobility and/or lower muscle function-adjusted covariates. Moreover, an inability to identify menthol and rose was associated with worse TUG (odds ratio [OR]: 0.424; 95% confidence interval [CI]: 0.215-0.836), star walking (OR: 0.714; 95% CI: 0.506-0.976), CS (OR: 0.638; 95% CI: 0.470-0.864), and vertical jump (OR: 1.12; 95% CI: 1.001-1.24) performance, even when the analysis was adjusted to exclude menthol and rose score from the overall olfaction score (p .05 for all).The current study may help to increase awareness of olfactory and physical dysfunction at an earlier stage among physically independent community-dwelling older adults.

Consumption of a high fat diet (HFD) and being overweight both induce functional deterioration and atrophy of the hippocampus. These alterations are associated with mental disorders such as depression and anxiety. Exercise combats obesity and enhances brain health. There is substantial evidence that neuronal nitric oxide synthase (nNOS) is a key regulator of affective behavior, and that increased brain nNOS leads to anxiety while environmental enrichment (EE), which reduces brain nNOS, has anxiolytic effects. In this study we investigated the effects of HFD with and without exercise on nNOS protein and gene expression levels in the brains of mice. Twelve weeks of HFD consumption increased body and mesenteric fat weight, as well as nNOS protein levels in the hippocampus and cerebral cortex. Six weeks of exercise training reduced body fat and rescued hippocampal and cortical nNOS expression levels in HFD-fed mice. Cerebellar nNOS expression was unaffected by HFD and exercise. Our results suggest that HFD-induced brain dysfunction may be regulated by hippocampal and/or cortical nNOS, and that exercise may have therapeutic potential for the treatment of HFD-induced depression and anxiety via the nNOS/NO pathway. In conclusion, exercise reverses HFD-induced changes in hippocampal and cortical nNOS protein levels in mice.

It has been suggested that breakfast omission, as opposed to breakfast consumption, has the detrimental effects on cognitive function. However, the effects of acute exercise following breakfast omission on cognitive function are poorly understood, particularly during exercise. The purpose of this study was to examine the interactive effects of breakfast and exercise on cognitive function. Ten participants completed cognitive tasks at rest and during exercise in the breakfast consumption or omission conditions. Blood glucose concentration was measured immediately after each cognitive task. We used cognitive tasks to assess working memory [Spatial Delayed Response (DR) task] and executive function [Go/No-Go (GNG) task]. The participants cycled ergometer for 30 min while keeping their heart rate at 140 beats·min(-1). Accuracy of the GNG task was lower at rest in the breakfast omission condition than that in the breakfast consumption condition (Go trial: P=0.012; No-Go trial: P=0.028). However, exercise improved accuracy of the Go trial in the breakfast omission condition (P=0.013). Reaction time in the Go trial decreased during exercise relative to rest in both conditions (P=0.002), and the degree of decreases in reaction time was not different between conditions (P=0.448). Exercise and breakfast did not affect the accuracy of the Spatial DR task. The present results indicate that breakfast omission impairs executive function, but acute exercise improved executive function even after breakfast omission. It appears that beneficial effects of acute exercise on cognitive function are intact following breakfast omission.

It has been suggested that acute exercise improves cognitive function. However, little is known about how exercise under hypoxia affects cognitive function. The purpose of this study was to determine if hypoxia alters working memory and executive function during prolonged exercise. Sixteen participants performed cognitive tasks at rest and during exercise under normoxia and hypoxia [fraction of inspired oxygen (FIO2) = 0.15, corresponding to an altitude of approximately 2600 m]. The level of hypoxia was moderate. We used a combination of Spatial Delayed Response (Spatial DR) task and Go/No-Go (GNG) task, where spatial working memory and executive function are required. Working memory was assessed by the accuracy of the Spatial DR task, and executive function was assessed by the accuracy and reaction time in the GNG task. The participants cycled an ergometer for 30 min under normoxia and moderate hypoxia while keeping their heart rate (HR) at 140 beats/min. They performed the cognitive tasks 5 min and 23 min after their HR reached 140 beats/min. Moderate hypoxia did not alter the accuracy of the Spatial DR (P = 0.38) and GNG tasks (P = 0.14). In contrast, reaction time in the GNG task significantly decreased during exercise relative to rest under normoxia and moderate hypoxia (P = 0.02). These results suggest that moderate hypoxia and resultant biological processes did not provide sufficient stress to impair working memory and executive function during prolonged exercise. The beneficial effects on speed of response appear to persist during prolonged exercise under moderate hypoxia.

Objective Studies using self-reported physical activity (PA) showed that higher PA is associated with lower circulating levels of C-reactive protein; in contrast, studies investigating associations of objective PA and other inflammatory markers are limited. We investigated cross-sectional associations of accelerometer-determined PA with circulating levels of myokine-type inflammatory cytokines in a middle-aged Japanese population. Method A total of 1838 individuals (737 men and 1101 women) aged 40 to 69 years participated in the baseline survey of a population-based cohort study in Saga, Japan (2005–2007). Habitual PA was assessed by a single-axis accelerometer. Serum interleukin (IL)-4, IL-6, IL-8, IL-15, and tumor necrosis factor (TNF)-α were measured by a multiplex enzyme-linked immunosorbent assay. Associations between PA and cytokine levels were assessed by multiple regression analysis and analysis of covariance, with adjustment for potential confounders. Results Step count and PA level (PAL) were inversely associated with TNF-α and IL-15 even after adjusting for BMI. Similarly, greater PA indices were also independently associated with a lower level of inflammatory cytokine z score as an index of overall inflammation. Conclusion The current results suggest that greater engagement in daily PA may be linked with reduced levels of myokine-type cytokines including IL-15, irrespective of body weight in middle-aged Japanese people.

Introduction Carnitine palmitoyltransferase II (CPT II) deficiency is an inherited disorder involving β-oxidation of long-chain fatty acids (FAO), which leads to rhabdomyolysis and subsequent acute renal failure. The detailed mechanisms of disease pathogenesis remain unknown; however, the availability of relevant human cell types for investigation, such as skeletal muscle cells, is limited, and the development of novel disease models is required. Methods We generated human induced pluripotent stem cells (hiPSCs) from skin fibroblasts of a Japanese patient with CPT II deficiency. Mature myocytes were differentiated from the patient-derived hiPSCs by introducing myogenic differentiation 1 (MYOD1), the master transcriptional regulator of myocyte differentiation. Using an in vitro acylcarnitine profiling assay, we investigated the effects of a hypolipidemic drug, bezafibrate, and heat stress on mitochondrial FAO in CPT II-deficient myocytes and controls. Results CPT II-deficient myocytes accumulated more palmitoylcarnitine (C16) than did control myocytes. Heat stress, induced by incubation at 38 °C, leads to a robust increase of C16 in CPT II-deficient myocytes, but not in controls. Bezafibrate reduced the amount of C16 in control and CPT II-deficient myocytes. Discussion In this study, we induced differentiation of CPT II-deficient hiPSCs into mature myocytes in a highly efficient and reproducible manner and recapitulated some aspects of the disease phenotypes of CPT II deficiency in the myocyte disease models. This approach addresses the challenges of modeling the abnormality of FAO in CPT II deficiency using iPSC technology and has the potential to revolutionize translational research in this field.

The purpose of the present study was to investigate the relationship among intra-abdominal adipose storage, adaptation in the serum leptin concentration and skeletal muscle enzyme activity after a 4-week energy restriction (ER). Thirty-one male Wistar rats were divided into 40% energy restricted (n=24) or ad libitum-fed control (CL) rats (n=7). The energy-restricted rats were grouped into the most fat (MF, n=7), medium (n 10) and the least fat (LF, n=7) by their intra-abdominal fat pads mass (epididymal, mesenteric, and perirenal) after ER. A superficial portion of M. gastrocnemius tissue obtained before and after the diet period were analyzed to determine the activities of hexokinase (HK), beta-hydroxyacyl CoA dehydrogenase (beta-HAD) and citrate synthase (CS). Blood samples were also collected for a serum leptin assay. At the baseline, no difference was found in either the leptin concentration or the enzyme activities among LF, MF and CL. The serum leptin concentration was positively correlated with the muscle activities of beta-HAD and CS, while it negatively correlated with HK/beta-HAD. After ER, the activities of HK, beta-HAD and CS were all significantly lower in LF than in CL. Among the energy-restricted rats, the intra-abdominal fat pad weight, leptin concentration and the activities of beta-HAD, CS, beta-HAD/CS all significantly correlated with one another. The changes in leptin and the activity of beta-HAD were also positively correlated. These findings indicate that parallel decreases in the serum leptin and skeletal muscle enzyme activities with the energy restriction-induced intra-abdominal adipose reduction, thus may suggest the leptin to have a regulative effect on the muscle enzyme activity during ER.

The relationships between skeletal muscle morphology, particularly muscle fiber capillary density, and serum lipid profiles were evaluated in 25 non-obese men aged 18 to 36 years (body mass index [BMI], 22.7 +/- 2.5 kg/m2; body fat, 13.6% +/- 4.0%, maximal oxygen uptake [VO2max], 46.2 < or = 6.3 mL/kg/min). Skeletal muscle samples were taken from the vastus lateralis using the needle-biopsy method. The fiber types (I, IIa, and IIx) and their percent distribution, the indices of capillary density, and the diffusion index expressed as the cross-sectional area occupied by one capillary were determined. Blood samples were drawn from the antecubital vein after a 12-hour fast. Based on Pearson's correlation analysis, the number of capillaries around type IIx fiber correlated inversely with the serum level of low-density lipoprotein cholesterol ([LDL-C] r = -.50, P < .05). The number of capillaries per fiber (cap/fiber ratio), number of capillaries per area (cap/mm2), and capillaries around each fiber type correlated inversely with the serum level of apolipoprotein B ([apo B] r = -.40 to -.54, P < .05 to .01). Further, the diffusion index for each fiber type correlated positively with LDL-C and apo B (r = .42 to .50, P < .05 to .01). Among 14 subjects in whom high-density lipoprotein cholesterol (HDL-C) subfractions were analyzed, a positive correlation was found between cap/mm2 and HDL2-C (r = .64, P < .05). Partial correlation analysis showed that these correlations either remain or improve after adjusting for age, VO2max, and body fatness. These results indicate that skeletal muscle capillary density and diffusion capacity are related to lipid and apolipoprotein concentrations for both type I and type II fibers.

Insulin receptor substrate-2-deficient (IRS2(-/-)) mice develop type 2 diabetes. The purpose of this study was to determine whether there is a defect in basal, insulin-, and exercise-stimulated glucose transport in the skeletal muscle of these animals. IRS2(-/-) and wild-type (WT) mice (male, 8-10 weeks) exercised on a treadmill for 1 h or remained sedentary. 2-Deoxyglucose (2DG) uptake was measured in isolated soleus muscles incubated in vitro in the presence or absence of insulin. Resting blood glucose concentration in IRS2(-/-) mice (10.3 mM) was higher than WT animals (4.1 mM), but there was a wide range among the IRS2(-/-) mice (3-25 mM). Therefore, IRS2(-/-) mice were divided into two subgroups based on blood glucose concentrations (IRS2(-/-)L7.2 mM, IRS2(-/-)H7.2 mM). Only IRS2(-/-)H had lower basal, exercise-, and submaximally insulin-stimulated 2DG uptake, while maximal insulin-stimulated 2DG uptake was similar among the three groups. The ED(50) for insulin to stimulate 2DG uptake above basal in IRS2(-/-)H was higher than WT and IRS2(-/-)L mice, suggesting insulin resistance in the skeletal muscle from the IRS2(-/-) mice with high blood glucose concentrations. Furthermore, resting blood glucose concentrations from all groups were negatively correlated to submaximally insulin-stimulated 2DG uptake (r(2) = 0.33, p0.01). Muscle GLUT4 content was significantly lower in IRS2(-/-)H mice compared with WT and IRS2(-/-)L mice. These results demonstrate that the IRS2 protein in muscle is not necessary for insulin- or exercise-stimulated glucose transport, suggesting that the onset of diabetes in the IRS2(-/-) mice is not due to a defect in skeletal muscle glucose transport; hyperglycemia may cause insulin resistance in the muscle of IRS2(-/-) mice.

To evaluate the effects of a single bout of exercise on non-insulin mediated glucose uptake in rats, hyperglycemic clamp tests were performed either 12 h after the rats were subjected to downhill running (90 min, -16 degrees incline, n = 10) or without any prior exercise (n = 10). Somatostatin (1.0 microgram/kg/min) was infused during clamps to suppress insulin secretion, while the serum glucose was clamped at a level of 200 mg/dl for 100 min. The serum insulin levels during the hyperglycemic clamp was maintained at basal levels. The non-insulin mediated glucose disposal rate was significantly decreased during clamp performed after downhill running (5.45 +/- 0.61 mg/kg/min) compared to the control conditions (9.63 +/- 0.32 mg/kg/min, P < 0.01). The creatine kinase level after downhill running (561 +/- 206 IU/l) was significantly higher than the control conditions (118 +/- 20 IU/l, P < 0.01). These results thus suggest that the muscle damage caused by downhill exercise, which predominantly consists of eccentric type, may therefore decrease the non-insulin mediated glucose uptake.