Effect of electromyostimulation on intramyocellular lipids of the vastus lateralis in older adults: a randomized controlled trial.

BACKGROUND: Excessive intramyocellular lipid (IMCL) accumulation is a primary cause of skeletal muscle insulin resistance, especially in older adults, and interventions that reduce IMCL contents are important to improve insulin sensitivity. Electromyostimulation (EMS)-induced changes in IMCL content in older adults remain unknown. The purpose of this study was to clarify the effects of a single bout of EMS on the IMCL content of the vastus lateralis muscle in older adults. METHODS: Twenty-two physically active, non-obese older men and women were randomly assigned to an EMS intervention group (69.0 ± 5.2 years, n = 12) or a control group (68.4 ± 3.5 years, n = 10). EMS was applied to the vastus lateralis (7 s on and 7 s off) for 30 min; control participants sat quietly for 30 min. IMCL content within the vastus lateralis was quantified with 1H-magnetic resonance spectroscopy (n = 7 per group). Fasting plasma glucose and insulin values were determined from blood samples collected before and after the EMS intervention. RESULTS: EMS induced a significant reduction in plasma glucose (93.1 ± 9.6 to 89.5 ± 9.1 mg/dL, p < 0.01), but not IMCL content (15.7 ± 15.7 to 15.8 ± 13.1 mmol/kg wet weight, p = 0.49) or insulin (5.4 ± 2.4 to 4.7 ± 2.7 µIU/mL, p = 0.18). In the control group, no changes in IMCL content in the vastus lateralis was observed after prolonged quiet sitting. CONCLUSION: EMS intervention for 30 min induces changes in plasma glucose, but no changes in IMCL content in older adults. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center ID: UMIN000020126 . Retrospectively registered on December 222,015. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000023242.

d-Allulose Ameliorates Skeletal Muscle Insulin Resistance in High-Fat Diet-Fed Rats.

BACKGROUND: d-Allulose is a rare sugar with antiobesity and antidiabetic activities. However, its direct effect on insulin sensitivity and the underlying mechanism involved are unknown. OBJECTIVE: This study aimed to investigate the effect of d-allulose on high-fat diet (HFD)-induced insulin resistance using the hyperinsulinemic-euglycemic (HE)-clamp method and intramuscular signaling analysis. METHODS: Wistar rats were randomly divided into three dietary groups: chow diet, HFD with 5% cellulose (HFC), and HFD with 5% d-allulose (HFA). After four weeks of feeding, the insulin tolerance test (ITT), intraperitoneal glucose tolerance test (IPGTT), and HE-clamp study were performed. The levels of plasma leptin, adiponectin, and tumor necrosis factor (TNF)-α were measured using the enzyme-linked immunosorbent assay. We analyzed the levels of cell signaling pathway components in the skeletal muscle using Western blotting. RESULTS: d-allulose alleviated the increase in HFD-induced body weight and visceral fat and reduced the area under the curve as per ITT and IPGTT. d-Allulose increased the glucose infusion rate in the two-step HE-clamp test. Consistently, the insulin-induced phosphorylation of serine 307 in the insulin receptor substrate-1 and Akt and expression of glucose transporter 4 (Glut-4) in the muscle were higher in the HFA group than HFC group. Furthermore, d-allulose decreased plasma TNF-α concentration and insulin-induced phosphorylation of stress-activated protein kinase/Jun N-terminal kinase in the muscle and inhibited adiponectin secretion in HFD-fed rats. CONCLUSIONS: d-allulose improved HFD-induced insulin resistance in Wistar rats. The reduction of the proinflammatory cytokine production, amelioration of adiponectin secretion, and increase in insulin signaling and Glut-4 expression in the muscle contributed to this effect.

Relationship between physical activity and intramyocellular lipid content is different between young and older adults.

PURPOSE: Intramyocellular lipid (IMCL) is influenced by physical exercise; however, whether the habitual level of physical activity affects resting IMCL content remains unclear. The purpose of this study was to determine the relationship between physical activity levels and resting IMCL content in young and older adults. METHODS: In total, 15 nonobese young adults (21.0 ± 0.0 years) and 15 older adults (70.7 ± 3.8 years) were recruited. Time spent performing physical activities for 10 days was assessed using a three-dimensional ambulatory accelerometer, and intensity was categorized as light [< 3.0 metabolic equivalents (METs)], moderate (3.0-6.0 METs), or vigorous (> 6.0 METs). Physical activity level was calculated as the product of METs and time spent performing physical activities (MET h) at each intensity level. The IMCL content in the vastus lateralis was determined using 1H-magnetic resonance spectroscopy after overnight fasting. RESULTS: No significant differences in IMCL content were observed between young and older adults. Vigorous intensity physical activity (time and MET h) was significantly lower in older than young adults (p < 0.01); this difference was not observed for light and moderate intensity physical activity. Light intensity physical activity (time and MET h) was significantly and inversely correlated with IMCL content in young adults (r = - 0.59 and r = - 0.58; both p < 0.05), but not in older adults. CONCLUSIONS: These results suggest that daily light intensity physical activity reduces resting IMCL content in young adults, whereas no significant relationship was seen between daily physical activity and resting IMCL content in older adults.

Elevated sympathetic vasomotor outflow in response to increased inspiratory muscle activity during exercise is less in young women compared with men.

NEW FINDINGS: What is the central question of this study? Premenopausal women have an attenuated inspiratory muscle metaboreflex-induced increase in arterial blood pressure compared with men. It is unclear whether sympathetic vasomotor outflow during dynamic exercise with increased inspiratory muscle activation is less in young women than in men. What is the main finding and its importance? The magnitude of increased sympathetic vasomotor outflow during leg cycling with inspiratory resistance was smaller in women than in men. Less sympathetic vasomotor outflow with inspiratory muscle metaboreflex activation could be one of the mechanisms for the attenuated inspiratory muscle-induced metaboreflex during exercise in young women. ABSTRACT: We compared changes in muscle sympathetic nerve activity (MSNA) and cardiovascular variables during leg cycle exercise with increased inspiratory muscle resistance in men and women. We hypothesized that sympathetic vasomotor outflow during exercise with increased inspiratory resistance would be attenuated in young women compared with age-matched men. Eight women and seven men completed the study. The subjects performed two 10 min exercise bouts at 40% peak oxygen uptake using a cycle ergometer in a semirecumbent position [spontaneous breathing for 5 min and voluntary hyperventilation with or without inspiratory resistive breathing for 5 min (breathing frequency 50 breaths min-1 with a 50% duty cycle; inspiratory resistance 30% of maximal inspiratory pressure)]. Mean arterial blood pressure (MAP) was acquired using finger photoplethysmography. The MSNA was recorded via microneurography of the right median nerve at the cubital fossa. During leg cycle exercise with inspiratory resistive breathing, MSNA burst frequency was increased, accompanied by an increase in MAP in both men and women. Women, compared with men, had less of an increase in MAP (women +22.8 ± 12.3 mmHg versus men +32.2 ± 5.4 mmHg; P < 0.05) and MSNA burst frequency (women +9.6 ± 2.9 bursts min-1 versus men +14.6 ± 6.4 bursts min-1 ; P < 0.05). These results suggest that the attenuated inspiratory muscle-induced metaboreflex during exercise in young women is attributable, in part, to a lesser sympathetic vasomotor outflow compared with men.

Muscle quality characteristics of muscles in the thigh, upper arm and lower back in elderly men and women.

PURPOSE: The ratio of fat within skeletal muscle is an important parameter that is indicative of muscle quality, and can be assessed using ultrasonography to measure echo intensity (EI). Muscle EI indicates muscle strength and risk of physical dysfunction; however, this observation was determined following examinations of only selected muscle. The purpose of this study was to investigate the EI characteristics of muscles in several regions in elderly men and women, using physical function tests and serum cholesterol levels. METHODS: Twenty-two men and women (age 78 ± 8 years) participated in this study. The EIs were calculated from rectus femoris (RF), biceps femoris (BF) triceps brachii (TB) and multifidus (MF) using B-mode transverse ultrasound images. Seven functional tests (isometric knee-extension peak torque, functional reach, sit-to-stand, 5-m normal/maximal speed walking, handgrip strength and timed up-and-go) and blood lipid components including adipocytokines were measured in all participants. RESULTS: A statistically significant correlation between EI of the RF, TB and BF was observed (r = 0.46-0.50, P < 0.05), but not between EI of the MF and that of other muscles. EI of muscles of the limbs, which was averaged EI for RF, TB and BF, was negatively correlated with leptin levels (adjusted R2 = 0.27, P < 0.01), and EI of the MF was correlated with muscle mass and performance in the timed up-and-go test (adjusted R2 = 0.61, P < 0.01). CONCLUSION: These results suggest that EI might be influenced by specific parameters depending on the location of the muscle.

Effects of post-fracture non-weight-bearing immobilization on muscle atrophy, intramuscular and intermuscular adipose tissues in the thigh and calf.

OBJECTIVE: Disuse and/or a non-weight-bearing condition changes muscle composition, with decreased skeletal muscle tissue and increased fat within (intramuscular adipose tissue, IntraMAT) and between (intermuscular adipose tissue, InterMAT) given muscles. Excessive adipose tissue contributes to dysfunctional and metabolically impaired muscle. How these adipose tissues change during orthopedic treatment (e.g., cast immobilization, daily use of crutches) is not well documented. This study aimed to quantify changes in IntraMAT, InterMAT, and thigh and calf muscle tissue during orthopedic treatment. MATERIALS AND METHODS: We studied 8 patients with fifth metatarsal bone or fibular fractures. The ankle joint involved underwent plaster casting for approximately 4 weeks, with crutches used during that time. Axial T1-weighted MRI at the mid-thigh and a 30% proximal site at the calf were obtained to measure IntraMAT and InterMAT cross-sectional areas (CSAs) and skeletal muscle tissue CSA before treatment and 4 weeks afterward. RESULTS: Thigh and calf muscle tissue CSAs were significantly decreased from before to after treatment: thigh, 85.8 ± 7.6 to 77.1 ± 7.3 cm2; calf, 53.3 ± 5.5 to 48.9 ± 5.0 cm2 (p < 0.05). None of the IntraMAT or InterMAT changes was statistically significant. There was a relation between the percentage change of thigh IntraMAT CSA and muscle tissue CSA (rs = -0.86, p < 0.01). CONCLUSIONS: The 4 weeks of treatment primarily induced skeletal muscle atrophy with less of an effect on IntraMAT or InterMAT. There is a risk of increasing IntraMAT relatively by decreasing skeletal muscle tissue size during orthopedic treatment.

Anti-pituitary antibodies against corticotrophs in IgG4-related hypophysitis.

PURPOSE: IgG4-related disease is a systemic inflammatory disease characterized by infiltration of IgG4-positive plasma cells into multiple organs, including the pituitary gland. Autoimmunity is thought to be involved in the pathogenesis of IgG4-related disease. The diagnosis of IgG4-related hypophysitis (IgG4-RH) is difficult because its clinical features, such as pituitary swelling and hypopituitarism, are similar to those of other pituitary diseases, including lymphocytic hypophysitis and sellar/suprasellar tumors. The presence and significance of anti-pituitary antibodies (APA) in IgG4-RH is unclear. METHODS: In this case-control study, we used single indirect immunofluorescence on human pituitary substrates to assess the prevalence of serum APA in 17 patients with IgG4-RH, 8 control patients with other pituitary diseases (lymphocytic infundibulo-neurohypophysitis, 3; craniopharyngioma, 2; germinoma, 3), and 9 healthy subjects. We further analyzed the endocrine cells targeted by the antibodies using double indirect immunofluorescence. RESULTS: APA were found in 5 of 17 patients with IgG4-RH (29%), and in none of the pituitary controls or healthy subjects. The endocrine cells targeted by the antibodies in the 5 IgG4-RH cases were exclusively corticotrophs. Antibodies were of the IgG1 subclass, rather than IgG4, in all 5 cases, suggesting that IgG4 is not directly involved in the pathogenesis. Finally, antibodies recognized pro-opiomelanocortin in 2 of the cases. CONCLUSIONS: Our study suggests that autoimmunity is involved in the pathogenesis of IgG4-RH and that corticotrophs are the main antigenic target, highlighting a possible new diagnostic marker for this condition.

Three-dimensional comparison of intramuscular fat content between young and old adults.

BACKGROUND: Fat infiltration within skeletal muscle is known as intramuscular fat (IMF), which increases with aging. Studies have assessed IMF content, using the mid-thigh as a representative location. However, three-dimensional IMF distribution is not well understood. The aim of this study was to compare the IMF content in young and old adults by assessing its distribution along the length of the thigh. METHODS: Consecutive transaxial images of the right thighs in 15 young (age, 21.0 ± 0.4) and 15 old (age, 70.7 ± 3.8) were obtained by magnetic resonance imaging. We measured IMF cross-sectional area (CSA), skeletal muscle CSA and calculated volume- and CSA-based IMF content for the quadriceps femoris (QF), hamstring (HM) and adductor (AD). CSA-based calculations were performed at every 10% of femur length (Lf), with 0% Lf and 100% Lf indicating the proximal and distal ends of femur. RESULTS: IMF CSAs along the length of the thigh were similar in both age groups. In contrast, skeletal muscle CSAs in all three muscle groups were significantly lower in old adults than in young adults (variation: -15.2 to -1.6 cm2, P < 0.05). Thus, in volume-based measurements, the older adults had higher IMF contents than the younger adults (9.5% to 14.3% vs. 4.8% to 8.6%, respectively; P < 0.05). However, such age-dependent differences were not observed at the mid-thigh in the QF and AD. CONCLUSION: The results demonstrated an age-related increase in IMF content-confirmed in areas of the thigh-primarily based on finding lower amounts of skeletal muscle mass in CSAs in the older adults.

Hypoxia attenuates cardiopulmonary reflex control of sympathetic nerve activity during mild dynamic leg exercise.

NEW FINDINGS: What is the central question of this study? The cardiopulmonary baroreflex inhibits adjustment of sympathetic vasomotor outflow during mild-intensity dynamic exercise. However, it is unclear how suppression of sympathetic vasomotor outflow by the cardiopulmonary baroreflex is modulated by a powerful sympatho-excitatory drive from the exercise pressor reflex, central command and/or the arterial chemoreflex. What is the main finding and its importance? Hypoxia-induced heightened sympathetic nerve activity during dynamic exercise attenuated cardiopulmonary baroreflex control of sympathetic vasomotor outflow. This could facilitate the redistribution of blood flow to the active muscles by sympathetically mediated vasoconstriction of inactive muscles. Muscle sympathetic nerve activity (MSNA) does not increase during mild-intensity dynamic leg exercise in normoxic conditions, despite activation of central command and the exercise pressor reflex. Suppression of MSNA could be caused by muscle pump-induced loading of cardiopulmonary baroreceptors. In contrast, MSNA increases during mild dynamic leg exercise in hypoxic conditions. We hypothesized that hypoxic exercise, which induces a powerful sympatho-excitatory drive from the exercise pressor reflex, central command and/or arterial chemoreflex, attenuates cardiopulmonary reflex control of sympathetic vasomotor outflow. To test this hypothesis, MSNA was recorded during leg cycling in hypoxic conditions and with increased central blood volume by increasing the pedalling frequency to change the cardiopulmonary baroreflex. Subjects performed two leg cycle exercises at different pedal cadences of 60 and 80 r.p.m. (60EX and 80EX trials, respectively) in two (haemodynamic and MSNA) measurement conditions while breathing a hypoxic gas mixture (inspired oxygen fraction = 0.12). Thoracic impedance, stroke volume and cardiac output were measured non-invasively using impedance cardiography. During the MSNA test, MSNA was recorded via microneurography at the right median nerve at the elbow. Changes in thoracic impedance, stroke volume and cardiac output during the 80EX trial were greater than those during the 60EX trial. The MSNA burst frequency during hypoxic exercise in the 80EX trial (39 ± 4 bursts min(-1)) did not differ from that during the 60EX trial (39 ± 3 bursts min(-1)). These results suggest that the cardiopulmonary baroreflex of sympathetic vasomotor outflow during dynamic exercise is modulated by heightened hypoxia-induced sympathetic nerve activity.

Skeletal muscle size is a major predictor of intramuscular fat content regardless of age.

PURPOSE: Skeletal muscles of older individuals have a larger amount of intramuscular adipose tissue (IntraMAT) than those of younger individuals. It is not understood how aging affects the IntraMAT content of individual muscles of the thigh. We assessed the relationship between IntraMAT content and skeletal muscle cross-sectional area (CSA), subcutaneous adipose tissue CSA, biochemical blood profiles, and physical activity. METHODS: Fifteen older (70.7 ± 3.8 years) and 15 younger (20.9 ± 0.3 years) men and women participated in this study. Magnetic resonance imaging of the right thigh was taken to measure IntraMAT content and skeletal muscle CSA for the quadriceps femoris (QF), hamstrings (HM), adductor (AD) muscle groups and subcutaneous adipose tissue CSA of the thigh. Fasting blood samples were collected to measure plasma lipids, adiponectin, and HbA1c levels. RESULTS: IntraMAT content in QF, HM, and AD for the Older group was significantly higher than in the Younger group. However, skeletal muscle CSA normalized by body weight (skeletal muscle CSA/bw) in the QF (P < 0.001) and total thigh (P < 0.01) were significantly lower in the Older group compared with the Younger group.There were no significant differences in HM and AD. Stepwise regression analysis with IntraMAT content as a dependent variable revealed that skeletal muscle CSA/bw of the thigh was the only predictive variable for IntraMAT content in Older and Younger groups. CONCLUSION: These results suggest that skeletal muscle size could be a major determinant of IntraMAT content regardless of age.

Association of skeletal muscle oxidative capacity with muscle function, sarcopenia-related exercise performance, and intramuscular adipose tissue in older adults.

Muscle function and exercise performance measures, such as muscle endurance capacity, maximal strength, chair stand score, gait speed, and Timed Up and Go score, are evaluated to diagnose sarcopenia and frailty in older individuals. Furthermore, intramuscular adipose tissue (IntraMAT) content increases with age. Skeletal muscle oxidative capacity determines muscle metabolism and maintains muscle performance. This study aimed to investigate the association of skeletal muscle oxidative capacity with muscle function, exercise performance, and IntraMAT content in older individuals. Thirteen older men and women participated in this study. Skeletal muscle oxidative capacity was assessed by the recovery speed of muscle oxygen saturation after exercise using near-infrared spectroscopy from the medial gastrocnemius. We assessed two muscle functions, peak torque and time to task failure, and four sarcopenia-related exercise performances: handgrip strength, gait speed, 30-s chair stand, and Timed Up and Go. The IntraMAT content was measured using axial magnetic resonance imaging. The results showed a relationship between skeletal muscle oxidative capacity and gait speed but not with muscle functions and other exercise performance measures. Skeletal muscle oxidative capacity was not related to IntraMAT content. Skeletal muscle oxidative capacity, which may be indicative of the capacity of muscle energy production in the mitochondria, is related to locomotive functions but not to other functional parameters or skeletal fat infiltration.

Hypoxic effects on sympathetic vasomotor outflow and blood pressure during exercise with inspiratory resistance.

The purpose of the present study was to clarify the influence of inspiratory resistive breathing during exercise under hypoxic conditions on muscle sympathetic nerve activity (MSNA) and blood pressure (BP). Six healthy males completed this study. The subjects performed a submaximal exercise test using a cycle ergometer in a semirecumbent position under normoxic [inspired oxygen fraction (FiO2) = 0.21] and hypoxic (FiO2 = 0.12-0.13) conditions. The subjects carried out two 10-min exercises at 40% peak oxygen uptake [spontaneous breathing for 5 min and voluntary breathing with inspiratory resistance for 5 min (breathing frequency: 60 breaths/min, inspiratory and expiratory times were set at 0.5 s each)]. MSNA was recorded via microneurography of the right median nerve at the elbow. A progressive increase in MSNA burst frequency (BF) during leg-cycling exercise with inspiratory resistance in normoxia and hypoxia were accompanied by an augmentation of BP. The increased MSNA BF and mean arterial BP (MBP) during exercise with inspiratory resistive breathing in hypoxia (MSNA BF, 55.7 ± 1.4 bursts/min, MBP, 134.3 ± 6.6 mmHg) were higher than those in normoxia (MSNA BF, 39.2 ± 1.8 bursts/min, MBP, 123.6 ± 4.5 mmHg). These results suggest that an enhancement of inspiratory muscle activity under hypoxic condition leads to large increases in muscle sympathetic vasomotor outflow and BP during dynamic leg exercise.

Inspiratory muscle fatigue increases sympathetic vasomotor outflow and blood pressure during submaximal exercise.

The purpose of this study was to elucidate the influence of inspiratory muscle fatigue on muscle sympathetic nerve activity (MSNA) and blood pressure (BP) response during submaximal exercise. We hypothesized that inspiratory muscle fatigue would elicit increases in sympathetic vasoconstrictor outflow and BP during dynamic leg exercise. The subjects carried out four submaximal exercise tests: two were maximal inspiratory pressure (PI(max)) tests and two were MSNA tests. In the PI(max) tests, the subjects performed two 10-min exercises at 40% peak oxygen uptake using a cycle ergometer in a semirecumbent position [spontaneous breathing for 5 min and with or without inspiratory resistive breathing for 5 min (breathing frequency: 60 breaths/min, inspiratory and expiratory times were each set at 0.5 s)]. Before and immediately after exercise, PI(max) was estimated. In MSNA tests, the subjects performed two 15-min exercises (spontaneous breathing for 5 min, with or without inspiratory resistive breathing for 5 min, and spontaneous breathing for 5 min). MSNA was recorded via microneurography of the right median nerve at the elbow. PI(max) decreased following exercise with resistive breathing, whereas no change was found without resistance. The time-dependent increase in MSNA burst frequency (BF) appeared during exercise with inspiratory resistive breathing, accompanied by an augmentation of diastolic BP (DBP) (with resistance: MSNA, BF +83.4%; DBP, +23.8%; without resistance: MSNA BF, +19.2%; DBP, -0.4%, from spontaneous breathing during exercise). These results suggest that inspiratory muscle fatigue induces increases in muscle sympathetic vasomotor outflow and BP during dynamic leg exercise at mild intensity.

Association between gait speed and bone strength in community-dwelling postmenopausal Japanese women.

OBJECTIVES: It is unclear whether gait speed can be used to predict bone status or to diagnose osteopenia or osteoporosis. The aim of our study was to determine whether the measurement of physical performance predicts bone strength in community-dwelling postmenopausal Japanese women. METHODS: We measured speed of sound (SOS), weight bearing index (WBI), maximum or usual gait speed, step length of each gait, single leg balance time with or without eyes closed, and grip strength among 1,061 postmenopausal women (mean age ± standard deviation 68 ± 8 years). RESULTS: After adjustments for age and body mass index, SOS was associated with maximum or usual gait speed and with step length during maximum speed gait, but not with WBI, grip strength, single-leg balance time with or without eyes closed, or step-length time during usual gait speed. When subjects were divided into quartile groups based on WBI (a marker of lower extremity strength), significant associations between usual or maximum gait speed and SOS were found only in the lowest and second lowest groups (first and second quartiles). Finally, analysis of sensitivity and specificity at various cut-off points of maximum gait speed to predict decreased SOS showed relatively high specificity compared with the corresponding sensitivity among those with low gait speed. CONCLUSIONS: Maximum gait speed together with WBI may be a useful and specific test to predict bone status in postmenopausal older women.

Contribution of skeletal muscle and serum lipids to muscle contraction induced by neuromuscular electrical stimulation in older individuals.

Intramyocellular lipids (IMCL) stored in droplets in muscle cells and free fatty acids (FFA) from fat cells in the blood are the main substrates of adenosine triphosphate during continuous muscle contractions of relatively lower intensity. Although it is known that the lipid oxidative capacity decreases with aging, the effect of IMCL and FFA on muscle contraction in older individuals remains unclear. The purpose of this study was to investigate the contribution of skeletal muscle lipids and blood lipids as energy sources for muscle contraction in older individuals. Eighteen older individuals (mean age: 70.4 ± 3.5 years) underwent muscle contraction intervention induced by intermittent neuromuscular electrical stimulation (NMES) to the vastus lateralis for 30 min. Fasting blood samples were obtained and proton magnetic resonance spectroscopy (1 H-MRS) was performed before and after NMES, and the parameters (including IMCL and extramyocellular lipid [EMCL]) from 1 H-MRS, along with FFA and adiponectin levels, were analyzed using the blood samples of all participants. Levels of IMCL and EMCL did not change (p > 0.05); however, FFA and adiponectin levels decreased from 1.1 ± 0.5 mEq/L to 0.8 ± 0.2 mEq/L and 12.0 ± 5.3 µg/ml to 11.4 ± 5.0 µg/ml, after NMES (p < 0.05), respectively. These findings indicate that serum lipids, but not skeletal muscle lipids, are the energy substrate utilized during involuntary muscle contraction in older individuals.

Relationship between adiponectin and intramuscular fat content determined by ultrasonography in older adults.

Age-associated intramuscular adipose tissue (IntraMAT) deposition induces the development of insulin resistance and metabolic syndrome. However, the relationship between IntraMAT and biochemical parameters in older adults remains unclear. The purpose of this study, therefore, was to elucidate the relationship between adiponectin and echo intensity-estimated IntraMAT using ultrasonography in normal-weight older adults (men 9, women 13) and examine biochemical parameters. Blood tests were performed to determine fasting levels of glucose, insulin, hemoglobin A1c, total cholesterol (Total-C), high-density-lipoprotein cholesterol, low-density-lipoprotein cholesterol (LDL-C), free fatty acid, triglycerides (TGs), adiponectin, leptin, high-sensitivity C-reactive protein, and high-sensitivity tumor necrosis factor, and homoeostasis model assessment index of insulin resistance (HOMA-IR). Mean gray-scale echo intensity was calculated as the IntraMAT index of the vastus lateralis. Waist circumference was measured at the level of the navel as the visceral adipose tissue (VAT) index. Echo intensity was significantly inversely correlated with adiponectin or LDL-C, and that was significantly positively correlated with TG. Adiponectin level was inversely correlated with waist circumference. Partial correlation analysis with waist circumference as the control variable revealed that adiponectin was inversely correlated with echo intensity, independent of waist circumference, whereas no such correlation was observed after controlling for LDL-C and TG levels. When biochemical parameters were grouped in the principal component analysis, among men, Total-C, insulin, and HOMA-IR or hemoglobin A1c, and high-sensitivity tumor necrosis factor-alpha were grouped with the same distribution for factors 1 and 2. Among women, glucose, insulin, HOMA-IR, and Total-C or TGs were grouped with the same distribution for factors 1 and 2. These data suggest that adiponectin level is related to IntraMAT content, independent of VAT in normal-weight older adults. The dynamics of adiponectin might not be similar to those of other circulating biochemical parameters in older men and women.

Importance of skeletal muscle lipid levels for muscle function and physical function in older individuals.

The skeletal muscle contains lipids inside (intramyocellular lipids, IMCL) or outside (extramyocellular lipids, EMCL) its cells. The muscle lipid content increases with age; however, the characteristics of IMCL and EMCL in older individuals are not well known. We aimed to examine the characteristics of skeletal muscle lipids by investigating their relationship with muscle function and physical functions. Seven elderly men and 16 elderly women participated. The skeletal muscle lipid content, including IMCL and EMCL, was measured in the vastus lateralis by proton magnetic resonance spectroscopy. Isometric knee extension with maximal voluntary contraction (MVC) and time-to-task failure for knee extension with 50% MVC were measured as muscle functions. The participants performed six physical function tests: preferred gait speed, maximal gait speed, Timed Up and Go, chair sit-to-stand, handgrip strength, and stand from the floor. The time to knee extension task failure had a significant relationship with the IMCL (rs = -0.43, P < 0.05), but not with the EMCL content. Significant relationships were confirmed in the EMCL content with the sit-to-stand (rs = -0.48, P < 0.05) and stand-from-the-floor (rs = 0.53, P < 0.05) tests. These findings indicated that muscle lipids are associated with muscle and physical functional performances in older individuals. Novelty: No relationship was confirmed between IMCL and EMCL in older individuals. Muscle endurance performance had a relationship with IMCL, but not with EMCL. Relationships between EMCL and physical functional tests (e.g., sit-to-stand and stand from the floor) were confirmed.

Factors related to trunk intramuscular adipose tissue content - A comparison of younger and older men.

The present study investigated factors related to trunk intramuscular adipose tissue (IntraMAT) content in younger and older men. Twenty-three healthy younger (20 to 29 years) and 20 healthy older men (63 to 79 years) participated in this study. The trunk IntraMAT content was measured using magnetic resonance imaging at the height of the 3rd lumbar vertebra. In addition to blood properties and physical performance, dietary intake was assessed by a self-administered diet history questionnaire. The dietary intake status was quantified using the nutrient adequacy score for the intake of 10 selected nutrients by summing the number of items that met the criteria of dietary reference intakes for Japanese individuals. The results obtained revealed that the trunk IntraMAT content was significantly higher in the older group than in the younger group (p < 0.05). In the younger group, the trunk IntraMAT content significantly correlated with systolic and diastolic blood pressure and HbA1c (rs = 0.443 to 0.464, p < 0.05). In the older group, significant and negative correlations were observed between the trunk IntraMAT content and 5-m usual walking speed, handgrip strength, and nutrient adequacy scores (rs = -0.485 to -0.713, p < 0.05). These results indicate that factors associated with the trunk IntraMAT content differed in an age dependent manner. In the younger group, the trunk IntraMAT content correlated with the metabolic status such as blood pressure and HbA1c. In the older group, physical performance and the dietary intake status negatively correlated with the trunk IntraMAT content.

Combined effects of exercise training and D-allulose intake on endurance capacity in mice.

This study investigated the combined effects of exercise training and D-allulose intake on endurance capacity in mice. Male C57BL/6J mice were fed either a control diet (Con) or a 3% D-allulose diet (Allu) and further divided into the sedentary (Sed) or exercise training (Ex) groups (Con-Sed, Con-Ex, Allu-Sed, Allu-Ex, respectively; n = 6-7/group). The mice in the Ex groups were trained on a motor-driven treadmill 5 days/week for 4 weeks (15-18 m/min, 60 min). After the exercise training period, all mice underwent an exhaustive running test to assess their endurance capacity. At 48 h after the running test, the mice in the Ex groups were subjected to run at 18 m/min for 60 min again. Then the gastrocnemius muscle and liver were sampled immediately after the exercise bout. The running time until exhaustion tended to be higher in the Allu-Ex than in the Con-Ex group (p = 0.08). The muscle glycogen content was significantly lower in the Con-Ex than in the Con-Sed group and was significantly higher in the Allu-Ex than in the Con-Ex group (p < 0.05). Moreover, exercise training increased the phosphorylation levels of adenosine monophosphate-activated protein kinase (AMPK) in the muscle and liver. The phosphorylation levels of acetyl coenzyme A carboxylase (ACC), a downstream of AMPK, in the muscle and liver were significantly higher in the Allu-Ex than in the Con-Sed group (p < 0.05), suggesting that the combination of exercise training and D-allulose might have activated the AMPK-ACC signaling pathway, which is associated with fatty acid oxidation in the muscle and liver. Taken together, our data suggested the combination of exercise training and D-allulose intake as an effective strategy to upregulate endurance capacity in mice. This may be associated with sparing glycogen content and enhancing activation of AMPK-ACC signaling in the skeletal muscle.

d-Allulose Improves Endurance and Recovery from Exhaustion in Male C57BL/6J Mice.

d-Allulose, a rare sugar, improves glucose metabolism and has been proposed as a candidate calorie restriction mimetic. This study aimed to investigate the effects of d-allulose on aerobic performance and recovery from exhaustion and compared them with the effects of exercise training. Male C57BL/6J mice were subjected to exercise and allowed to run freely on a wheel. Aerobic performance was evaluated using a treadmill. Glucose metabolism was analyzed by an intraperitoneal glucose tolerance test (ipGTT). Skeletal muscle intracellular signaling was analyzed by Western blotting. Four weeks of daily oral administration of 3% d-allulose increased running distance and shortened recovery time as assessed by an endurance test. d-Allulose administration also increased the maximal aerobic speed (MAS), which was observed following treatment for >3 or 7 days. The improved performance was associated with lower blood lactate levels and increased liver glycogen levels. Although d-allulose did not change the overall glucose levels as determined by ipGTT, it decreased plasma insulin levels, indicating enhanced insulin sensitivity. Finally, d-allulose enhanced the phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase and the expression of peroxisome proliferator-activated receptor γ coactivator 1α. Our results indicate that d-allulose administration enhances endurance ability, reduces fatigue, and improves insulin sensitivity similarly to exercise training. d-Allulose administration may be a potential treatment option to alleviate obesity and enhance aerobic exercise performance.