Niacin supplementation attenuates the regression of three-dimensional capillary architecture in unloaded female rat skeletal muscle.

Inactivity can lead to muscle atrophy and capillary regression in skeletal muscle. Niacin (NA), known for inducing hypermetabolism, may help prevent this capillary regression. In this study involving adult female Sprague-Dawley rats, the animals were randomly assigned to one of four groups: control (CON), hindlimb unloading (HU), NA, and HU with NA supplementation (HU + NA). For a period of 2 weeks, the rats in the HU and HU + NA groups underwent HU, while those in the NA and HU + NA groups received NA (750 mg/kg) twice daily through oral administration. The results demonstrated that HU lowered capillary number, luminal diameter, and capillary volume, as well as decreased succinate dehydrogenase activity, slow fiber composition, and PGC-1α expression within the soleus muscle. However, NA supplementation prevented these alterations in capillary structure due to unloading by stimulating PGC-1α factors and inhibiting mitochondrial dysfunction. Therefore, NA supplementation could serve as a potential therapeutic approach for preserving the capillary network and mitochondrial metabolism of muscle fibers during periods of inactivity.

Time elapsed from definitive diagnosis to surgery for osteonecrosis of the femoral head: a nationwide observational study in Japan.

OBJECTIVES: This study documents the time elapsed from the diagnosis of osteonecrosis of the femoral head (ONFH) to surgery, exploring the factors that influence ONFH severity. DESIGN: Retrospective observational study of a nationwide database. SETTING: The Kaplan-Meier method with log-rank tests was applied to examine the period from definitive diagnosis of ONFH to surgery using any surgery as the end point. For bilateral cases, the date of the first surgery was the endpoint. PARTICIPANTS: This study included 2074 ONFH cases registered in 34 university hospitals and highly specialised hospitals of the multicentre sentinel monitoring system of the Japanese Investigation Committee between 1997 and 2018. MAIN OUTCOME MEASURE: The primary outcome was the time from diagnosis to surgery. The secondary outcome was the proportion of subjects remaining without surgery at 3, 6 and 9 months, and at 1, 2 and 5 years after diagnosis. RESULTS: The median time to surgery was 9 months (IQR 4-22 months) after diagnosis of ONFH. The time to surgery was significantly shorter in the alcohol alone group and the combined corticosteroid and alcohol group than in the corticosteroid alone group (p=0.018 and p<0.001, respectively), in early stage ONFH with no or mild joint destruction (stages II and III, p<0.001), and with joint preserving surgery (p<0.001). The proportion without surgery was 75.8% at 3 months, 59.6% at 6 months, 48.2% at 9 months, 40.5% at 1 year, 22.2% at 2 years and 8.3% at 5 years. CONCLUSION: ONFH has been considered to be an intractable disease that often requires surgical treatment, but the fact that surgery was performed in more than half of the patients within 9 months from diagnosis suggests severe disease with a significant clinical impact. TRIAL REGISTRATION NUMBER: Chiba University ID1049.

Effects of interleukin-15 on autophagy regulation in the skeletal muscle of mice.

This study aimed to evaluate the role of skeletal muscle-derived interleukin (IL)-15 in the regulation of skeletal muscle autophagy using IL-15 knockout (KO) and transgenic (TG) mice. Male C57BL/6 wild-type (WT), IL-15 KO, and IL-15 TG mice were used in this study. Changes in muscle mass, forelimb grip strength, succinate dehydrogenase (SDH) activity, gene and protein expression levels of major regulators and indicators of autophagy, comprehensive gene expression, and DNA methylation in the gastrocnemius muscle were analyzed. Enrichment pathway analyses revealed that the pathology of IL-15 gene deficiency was related to the autophagosome pathway. Moreover, although IL-15 KO mice maintained gastrocnemius muscle mass, they exhibited a decrease in autophagy induction. IL-15 TG mice exhibited a decrease in gastrocnemius muscle mass and an increase in forelimb grip strength and SDH activity in skeletal muscle. In the gastrocnemius muscle, the ratio of phosphorylated adenosine monophosphate-activated protein kinase α (AMPKα) to total AMPKα and unc-51-like autophagy activating kinase 1 and Beclin1 protein expression were higher in the IL-15 TG group than in the WT group. IL-15 gene deficiency induces a decrease in autophagy induction. In contrast, IL-15 overexpression could improve muscle quality by activating autophagy induction while decreasing muscle mass. The regulation of IL-15 in autophagy in skeletal muscles may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.NEW & NOTEWORTHY IL-15 gene deficiency can decrease autophagy induction. However, although IL-15 overexpression induced a decrease in muscle mass, it led to an improvement in muscle quality. Based on these results, understanding the role of IL-15 in regulating autophagy pathways within skeletal muscle may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.

Alternating current electromagnetic field exposure lessens intramyocellular lipid accumulation due to high-fat feeding via enhanced lipid metabolism in mice.

Long-term high-fat feeding results in intramyocellular lipid accumulation, leading to insulin resistance. Intramyocellular lipid accumulation is related to an energy imbalance between excess fat intake and fatty acid consumption. Alternating current electromagnetic field exposure has been shown to enhance mitochondrial metabolism in the liver and sperm. Therefore, we hypothesized that alternating current electromagnetic field exposure would ameliorate high-fat diet-induced intramyocellular lipid accumulation via activation of fatty acid consumption. C57BL/6J mice were either fed a normal diet (ND), a normal diet and exposed to an alternating current electromagnetic field (ND+EMF), a high-fat diet (HFD), or a high-fat diet and exposed to an alternating current electromagnetic field (HFD+EMF). Electromagnetic field exposure was administered 8 hrs/day for 16 weeks using an alternating current electromagnetic field device (max.180 mT, Hokoen, Utatsu, Japan). Tibialis anterior muscles were collected for measurement of intramyocellular lipids, AMPK phosphorylation, FAT/CD-36, and carnitine palmitoyltransferase (CPT)-1b protein expression levels. Intramyocellular lipid levels were lower in the HFD + EMF than in the HFD group. The levels of AMPK phosphorylation, FAT/CD-36, and CPT-1b protein levels were higher in the HFD + EMF than in the HFD group. These results indicate that alternating current electromagnetic field exposure decreases intramyocellular lipid accumulation via increased fat consumption.

High-Degree Valgus Osteotomy for Severe Femoral Head Osteonecrosis After Femoral Neck Fracture with Nonunion: A Case Report.

CASE: A 15-year-old adolescent boy had severe groin pain because of extensive osteonecrosis of the femoral head with collapse, joint space narrowing, and nonunion after a failed internal fixation for femoral neck fracture. We performed a 60° valgus osteotomy that moved the posteromedial small viable portion of the femoral head to the weight-bearing acetabular area. The femoral neck nonunion and the necrosis healed completely, and the spherical contour of the femoral head was regained after postoperative hip joint remodeling. CONCLUSIONS: Good remodeling and congruency were achieved by performing high-degree valgus osteotomy to obtain sufficient viable area below the acetabular roof.

High-degree posterior rotational osteotomy for extensive collapsed femoral head osteonecrosis in teenagers: remodeling and results with a mean of 10-year follow-up.

INTRODUCTION: This study evaluated the effectiveness of high-degree posterior rotational osteotomy for teenagers with extensively collapsed femoral head osteonecrosis. MATERIALS AND METHODS: We reviewed 40 hips in 35 patients with severely collapsed femoral head osteonecrosis treated by this procedure with a mean follow-up period of 9.7 years (range 5-25 years). Thirteen hips had a history of steroid administration. Nine had slipped capital femoral epiphysis. Nine had femoral neck fracture. Two had traumatic dislocation and fracture. Seven had no apparent risk factors. The mean age of the patients (18 women and 17 men) was 14.8 years. All femoral heads were extensively collapsed below the acetabular roof, and 20 hips showed preoperative joint space narrowing (ARCO stage 4). Lateral radiographs of the femoral head revealed extensive lesions from the posterior to anterior portion. The mean degree of posterior rotation was 118° with intentional varus positioning [mean: 19° (range 10-30)]. The pre- and postoperative extent of the viable area of the femoral head was assessed using conventional anteroposterior radiographs and 45-degree flexion radiography. Further collapse, joint space narrowing, femoral head morphology, and congruency with the acetabulum based on the Stulberg classification were assessed using conventional anteroposterior radiographs. The clinical assessment was conducted using the Merle d'Aubigné hip scores at the last follow-up. RESULTS: The viable area of the femoral head on the loaded portion was seen during a short period after operations. The necrotic lesions were gradually improved postoperatively. The mean extent of viable bone below the acetabular roof was 48% at less than 6 months after surgery and 92% at the final follow-up. The mean extent on 45° flexion radiography was 54% at less than 6 months after surgery and 89% at the final follow-up. Further collapse was prevented in 38 hips (95%). In 19 of 20 hips with preoperative narrowing of the joint space, the joint space was first improved, but narrowing progressively observed in 9 of 40 hips at the final follow-up. Thirty-four hips had excellent or good clinical outcomes, whereas 6 had fair or poor outcomes. CONCLUSIONS: We concluded that this procedure is effective at delaying the progression of degeneration if adequate area of viable bone can be moved under the loaded portion of the acetabulum in teenagers with severe femoral head osteonecrosis.

Mild Hyperbaric Oxygen Exposure Enhances Peripheral Circulatory Natural Killer Cells in Healthy Young Women.

Mild hyperbaric oxygen (HBO) enhances oxygen absorption in blood, relieving fatigue without causing oxidative stress. The benefits of mild HBO have been recognized in the treatment of lifestyle-related diseases and hypertension, but no research has been conducted on its effects on immunity. The aim of the present study is to investigate the effect of mild HBO on natural killer (NK) cells and cytokines in healthy young women. This crossover randomized control trial was conducted with 16 healthy young women. Participants were randomly exposed to normobaric oxygen (NBO; 1.0 atmospheres absolute (ATA), 20.8% oxygen) and mild HBO conditions (1.4 ATA, 35-40% oxygen, injected 18L oxygen per minute) in a hyperbaric oxygen chamber for 70 min. Heart rate, parasympathetic activity, NK cell count, interleukin (IL)-6, IL-12p70 and derivatives of reactive oxygen metabolites (d-ROMs) were measured before and after both exposures. In the NBO condition, parasympathetic activity remained unchanged, whereas after mild HBO exposure, parasympathetic activity was significantly increased. NK cells remained unchanged after NBO exposure, while NK cells were increased after exposure to mild HBO. Exposure to mild HBO did not increase d-ROM values, IL-6 and IL-12p70 protein levels. These findings suggest that exposure to mild HBO can be a useful protocol to increase NK cells by regulating parasympathetic activity via increasing oxygen delivery.

Brazilian Propolis Intake Decreases Body Fat Mass and Oxidative Stress in Community-Dwelling Elderly Females: A Randomized Placebo-Controlled Trial.

This study aimed to investigate the effects of Brazilian propolis on body fat mass and levels of adiponectin and reactive oxygen species among community-dwelling elderly females. This was a double-blind randomized placebo-controlled trial. Altogether, 78 females aged 66-84 years were randomly assigned to the propolis (PRO; n = 39) or placebo (PLA; n = 39) group. For 12 weeks, the PRO group were given three capsules containing 227 mg of propolis twice a day. Meanwhile, the PLA group were given daily placebo capsules. Of 78 participants, 53 (PLA group: n = 28, PRO group: n = 25) completed the study. Although no changes were observed in absolute or relative fat mass in the PLA group, they showed a significant decline in the PRO group. The level of serum adiponectin in the PLA group did not change, although that of the PRO group significantly increased. The level of d-ROMs in the PLA group significantly increased, whereas that of the PRO group significantly decreased. The serum SOD activity in the PLA group significantly decreased, whereas that of the PRO group tended to increase. These results suggest that propolis supplementation may decrease body fat mass and oxidative stress among community-dwelling elderly females.

High Concentrations of Nucleotides Prevent Capillary Regression during Hindlimb Unloading by Inhibiting Oxidative Stress and Enhancing Mitochondrial Metabolism of Soleus Muscles in Rats.

Prolonged inactivity in skeletal muscles decreases muscle capillary development because of an imbalance between pro- and antiangiogenic signals, mitochondrial metabolism disorders, and increased oxidative stress. Nucleotides have been shown to exert a dose-dependent effect on disuse-induced muscle atrophy. However, the dose-dependent effect on capillary regression in disused muscles remains unclear. Therefore, this study investigated the dose-dependent effect of nucleotides on capillary regression due to disuse. For this purpose, Wistar rats were divided into five groups as follows: control rats fed nucleotide-free diets (CON), hindlimb-unloaded rats fed nucleotide-free diets (HU), and hindlimb-unloaded rats fed 1.0%, 2.5%, and 5.0% nucleotide diets, (HU + 1.0% NT), (HU + 2.5% NT), and (HU + 5.0% NT), respectively. Unloading increased reactive oxygen species (ROS) production and decreased mitochondrial enzyme activity, thereby decreasing the number of muscle capillaries. In contrast, 5.0% nucleotide-containing diet prevented increases in ROS production and reductions in the expression levels of NAMPT, PGC-1α, and CPT-1b proteins. Moreover, 5.0% nucleotide-containing diet prevented mitochondrial enzyme activity (such as citrate synthase and beta-hydroxy acyl-CoA dehydrogenase activity) via NAMPT or following PGC-1α upregulation, thereby preventing capillary regression. Therefore, 5.0% nucleotide-containing diet is likely to prevent capillary regression by decreasing oxidative stress and increasing mitochondrial metabolism.

Impacts of Astaxanthin Supplementation on Walking Capacity by Reducing Oxidative Stress in Nursing Home Residents.

Oxidative stress is associated with deterioration of endurance and muscle strength, which are mostly accompanied by aging. Astaxanthin supplement has excellent antioxidant activity without any pro-oxidative properties. In this study, we investigated how astaxanthin supplementation affects walking endurance and muscle strength in nursing home residents. Healthy elderly individuals (age: 67 to 94) were divided into two groups: 13 subjects received a daily dose of 24 mg of astaxanthin for 16 weeks (astaxanthin group) and 11 subjects received a placebo (placebo group). These subjects were compared using body component measurements, serum d-ROM levels, the distance of 6-min walking, blood lactate levels after the 6-min walking test, and muscle strength. After supplementation, the levels of d-ROMs and blood lactate after the 6-min walking test in the astaxanthin group significantly decreased compared with the placebo group (p < 0.05). Additionally, the walking distance was significantly higher in the astaxanthin group than in the placebo group (p < 0.05), despite a significant reduction in lactate levels after 6-MWT (p < 0.05). However, no significant intergroup differences were observed in muscle mass and strength. Astaxanthin supplement for 16 weeks is effective to increase the endurance capacity of the elderly. Astaxanthin supplement suppresses d-ROMs at rest and lactic acid production after the 6-min walk test. In contrast, astaxanthin supplement did not show significant intergroup differences in the muscle mass and strength. Therefore, the effect was most likely accompanied by an increase in endurance instead of an increase in muscle strength.

Direct Probe of the Ferromagnetic Proximity Effect at the Interface of SnTe/Fe Heterostructure by Polarized Neutron Reflectometry.

Introducing magnetic order into a topological insulator (TI) system has attracted much attention with an expectation of realizing exotic phenomena such as the quantum anomalous Hall effect (QAHE) and axion insulator states. The magnetic proximity effect (MPE) is one of the promising schemes to induce the magnetic order on the surface of a TI without introducing disorder accompanied by doping magnetic impurities in the TI. In this study, we investigate the MPE at the interface of a heterostructure consisting of the topological crystalline insulator (TCI) SnTe and Fe by employing polarized neutron reflectometry. The ferromagnetic order penetrates ∼2.2 nm deep into the SnTe layer from the interface with Fe, which persists up to room temperature. This is induced by the MPE on the surface of the TCI preserving the coherent topological states without introducing the disorder by doping magnetic impurities. This would open up a way for realizing next-generation spintronics and quantum computational devices.

Soft-Magnetic Skyrmions Induced by Surface-State Coupling in an Intrinsic Ferromagnetic Topological Insulator Sandwich Structure.

A magnetic skyrmion induced on a ferromagnetic topological insulator (TI) is a real-space manifestation of the chiral spin texture in the momentum space and can be a carrier for information processing by manipulating it in tailored structures. Here, a sandwich structure containing two layers of a self-assembled ferromagnetic septuple-layer TI, Mn(Bi1-xSbx)2Te4 (MnBST), separated by quintuple layers of TI, (Bi1-xSbx)2Te3 (BST), is fabricated and skyrmions are observed through the topological Hall effect in an intrinsic magnetic topological insulator for the first time. The thickness of BST spacer layer is crucial in controlling the coupling between the gapped topological surface states in the two MnBST layers to stabilize the skyrmion formation. The homogeneous, highly ordered arrangement of the Mn atoms in the septuple-layer MnBST leads to a strong exchange interaction therein, which makes the skyrmions "soft magnetic". This would open an avenue toward a topologically robust rewritable magnetic memory.

Amiloride is a suitable fluorescent substrate for the study of the drug transporter human multidrug and toxin extrusion 1 (MATE1).

Human multidrug and toxin extrusion 1 (MATE1; SLC47A1) is highly expressed in the kidneys and the liver. It plays a significant role in drug and endogenous compound disposition, and therefore, a rapid evaluation of its inhibition is important for drug development and for the understanding of renal and hepatic physiology. Amiloride is a potassium-sparing diuretic used for treating hypertension; it also demonstrates strong fluorescence in organic solvent or detergent solutions. In this study, we investigated the transport characteristics of amiloride by human MATE1. Cellular accumulation of amiloride was evaluated in control vector- or MATE1-transfected HEK293 cells. Cells were lysed with 1% sodium dodecyl sulfate, and fluorescence was measured using a microplate reader at wavelengths of 364ex and 409em. With ammonium prepulse-induced intracellular acidification, MATE1 transported amiloride at an extracellular pH of 7.4. The uptake demonstrated an overshoot phenomenon and saturated, with the Km and Vmax being 23.5 µM and 1.01 nmol/mg/min, respectively. MATE1-mediated amiloride transport also presented with a bell-shaped pH profile that reached a maximum pH value of 7.4. The inhibitor sensitivity of MATE1-facilitated amiloride transport was similar to those of known substrates, such as tetraethylammonium and metformin. Among the tested inhibitors, pyrimethamine demonstrated the most potent inhibition with an IC50 value of 0.266 µM. Furthermore, MATE1 was found to be inhibited by fampridine, which was previously considered to be a non-inhibitor of MATE1. This study demonstrates that amiloride is a suitable fluorescent substrate for the in vitro study of the transport activity of MATE1.

Effects of porous tantalum on periprosthetic bone remodeling around metaphyseal filling femoral stem: a multicenter, prospective, randomized controlled study.

Periprosthetic bone loss due to adaptive bone remodeling is an important unresolved issue in cementless total hip arthroplasty (THA). The use of porous tantalum on the proximal surface of the femoral stem is expected to decrease postoperative bone loss around the prosthesis through early fixation. We conducted a multicenter randomized controlled study to determine if porous tantalum could reduce periprosthetic bone loss after THA. From October 2012 to September 2014, 118 patients (mean age, 61.5 years; 107 females and 11 males) were prospectively enrolled and were randomly allocated at a ratio of 1:1 to either a metaphyseal filling stem with a proximal porous tantalum coating (Trabecular Metal) or a conventional metaphyseal filling stem with fiber mesh coating (VerSys). Patients underwent dual-energy x-ray absorptiometry scans within 1 week after surgery (baseline) and at 6, 12, and 24 months after surgery to assess periprosthetic bone mineral density (BMD) in the 7 Gruen zones. In addition, the Japanese Orthopaedic Association hip score was assessed before surgery and at 6, 12, and 24 months after surgery. In the proximal periprosthetic region (zones 1 and 7), the Trabecular Metal group had significantly smaller reductions in BMD than the VerSys group throughout the study period. In the VerSys group, significant reductions in BMD compared to baseline were seen at each measurement point in all regions, except in zone 6 at 24 months. In the Trabecular Metal group, no significant reductions in BMD relative to baseline were seen in zones 1, 5, or 6 throughout the study period. Both groups demonstrated similar improvement in Japanese Orthopaedic Association hip scores over the study period. This study demonstrated that a proximally coated stem with porous tantalum has superior results over a conventional stem with titanium fiber mesh in terms of periprosthetic bone remodeling.

Protective effects of chlorogenic acid on capillary regression caused by disuse muscle atrophy.

Inactivity causes muscle atrophy and capillary regression in skeletal muscle. Chlorogenic acid has an antioxidant capacity and may prevent capillary regression. Therefore, the protective effects of chlorogenic acid on inactivity-induced capillary regression in rat soleus muscle were investigated. Twenty male Wistar rats were randomly divided into four groups: control (CON), chlorogenic acid supplementation (CGA), 2-week hindlimb unloading (HU), 2-week hindlimb unloading plus chlorogenic acid supplementation (HU+CGA). The rats in CGA and HU+CGA groups were orally administrated chlorogenic acid (850 mg/kg/day). Unloading resulted in a decrease in capillary number, oxidative capacity, and an increase in oxidative stress of the soleus muscle, whereas chlorogenic acid supplementation prevented capillary and metabolic changes resulting from unloading by reducing oxidative stress. In conclusion, chlorogenic acid supplementation may qualify as an effective treatment to reduce capillary regression in skeletal muscle caused by disuse muscle atrophy.

Effects of combined treatment with blood flow restriction and low-current electrical stimulation on capillary regression in the soleus muscle of diabetic rats.

To clarify the preventive effects of low-current electrical stimulation (ES) under blood flow restriction (Bfr) on diabetes-associated capillary regression in skeletal muscles, we assessed the changes in three-dimensional capillary architecture and angiogenic factors. Twenty-four Goto-Kakizaki rats were randomly divided into four groups: the sedentary diabetes mellitus (DM), Bfr (DM + Bfr), electrical stimulation (DM + ES), and Bfr plus ES (DM + Bfr + ES) groups. Six healthy Wistar rats were used as age-matched controls. Bfr was performed using pressure cuffs (80 mmHg) around the thighs of the rats, and low-current ES was applied to the calf muscles of the rats. The current intensity was set at 30% of the maximal isometric contraction (24-30 mA). The treatments were delivered three times a week for 8 wk. In the DM group, the capillary diameter and volume of the soleus muscle decreased, and, the antiangiogenic factor level increased. Furthermore, DM caused an increase in the hypoxia-inducible factor. Individually, Bfr or ES treatments failed to inhibit the DM-associated capillary regression and increase in antiangiogenic factor. However, combined treatment with Bfr and ES prevented DM-associated capillary regression via inhibition of the increased antiangiogenic factor and enhancement of interleukin-15 expression, mitochondrial biogenesis factors, and a proangiogenic factor. Therefore, DM-associated capillary regression inhibited by the combined treatment may prevent the effects of the increased antiangiogenic factor and enhance the proangiogenic factor.NEW & NOTEWORTHY The combined treatment of blood flow restriction and low intensity electrical stimulation attenuated type 2 diabetes (T2D)-associated capillary regression in the skeletal muscles. The treatment inhibits the T2D-associated increase in antiangiogenic factors via inhibition of intramuscular chronic hypoxia; it can inhibit intramuscular chronic hypoxia by enhancing proangiogenic factors. These results suggest that the combined treatment may be an effective therapeutic intervention for the prevention of T2D-associated capillary regression in the skeletal muscles.

Protective effects of Enterococcus faecium strain R30 supplementation on decreased muscle endurance under disuse in rats.

NEW FINDINGS: What is the central question of this study? Does Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, attenuate shifts in the typology of whole muscle fibres from slow- to fast-twitch by altering the autonomic nervous system in atrophied skeletal muscles? What is the main finding and its importance? R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres by upregulating peroxisome proliferator-activated receptor-γ coactivator-1α and activating the calcineurin-nuclear factor of activated T-cells signalling pathway, thus ameliorating the decrease in muscle endurance associated with disuse. ABSTRACT: Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, was hypothesized to attenuate shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres in atrophied skeletal muscles. We further postulated that the prevention of slow-to-fast fibre shifts would suppress the decreased muscle endurance associated with atrophy. To evaluate the protective effects of R30, we analysed slow-to-fast fibre shifts and disuse-associated reduced muscle endurance. R30 was administered to rats with an acclimation period of 7 days before hindlimb unloading (HU) for 2 weeks. The composition ratio of the fibre type and the expression levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), calcineurin and nuclear factor of activated T-cells (NFAT) were measured. Muscle endurance was evaluated at the end of the 2-week HU period in an in situ environment. R30 supplementation suppressed the slow-to-fast fibre switch and decreased the HU-induced expression of PGC-1α proteins and the deactivation of the calcineurin-NFAT pathway. Furthermore, R30 prevented a decrease in HU-associated muscle endurance in calf muscles. These results indicate that R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres via the upregulation of PGC-1α and the activation of the calcineurin-NFAT signalling pathway, thereby ameliorating the decrease in muscle endurance associated with disuse.

Nucleoprotein-enriched diet enhances protein synthesis pathway and satellite cell activation via ERK1/2 phosphorylation in unloaded rat muscles.

NEW FINDINGS: What is the central question of this study? The purpose of this study was to determine whether the nucleotides in a nucleoprotein-enriched diet could ameliorate the unloading-associated decrease in soleus muscle mass and fibre size. What is the main finding and its importance? The results indicate that the nucleotides in the nucleoprotein-enriched diet could ameliorate the unloading-associated decrease in type I fibre size and muscle mass, most probably owing to the activation of protein synthesis pathways and satellite cell proliferation and differentiation via ERK1/2 phosphorylation. Thus, nucleotide supplementation appears to be an effective countermeasure for muscle atrophy. ABSTRACT: Hindlimb unloading decreases both the protein synthesis pathway and satellite cell activation and results in muscle atrophy. Nucleotides are included in nucleoprotein and provide the benefits of increasing extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. ERK1/2 phosphorylation is also important in the activation of satellite cells, especially for myoblast proliferation and stimulating protein synthesis pathways. Therefore, we hypothesized that nucleotides in the nucleoproteins would ameliorate muscle atrophy by increasing the protein synthesis pathways and satellite cell activation during hindlimb unloading in rat soleus muscle. Twenty-four female Wistar rats were divided into four groups: control rats fed a basal diet without nucleoprotein (CON), control rats fed a nucleoprotein-enriched diet (CON+NP), hindlimb-unloaded rats fed a basal diet (HU) or hindlimb-unloaded rats fed a nucleoprotein-enriched diet (HU+NP). HU for 2 weeks resulted in reductions in phosphorylation of p70S6K and rpS6, the numbers of myoblast determination protein (MyoD)- and myogenin- positive nuclei, type I muscle fibre size and muscle mass. Both CON+NP and HU+NP rats showed an increase in ERK1/2, phosphorylation of p70S6K and rpS6, and the numbers of MyoD- and myogenin-positive nuclei compared with their basal diet groups. The NP diet also ameliorated the unloading-associated decrease in type I muscle fibre size and muscle mass. The results indicate that the nucleotides in the nucleoprotein-enriched diet could ameliorate the unloading-associated decrease in type I fibre size and muscle mass, most probably owing to the activation of protein synthesis pathways and satellite cell proliferation and differentiation via ERK1/2 phosphorylation. Thus, nucleotide supplementation appears to be an effective countermeasure for muscle atrophy.

Reduced metabolic capacity in fast and slow skeletal muscle via oxidative stress and the energy-sensing of AMPK/SIRT1 in malnutrition.

The effects of malnutrition on skeletal muscle result in not only the loss of muscle mass but also fatigue intolerance. It remains unknown whether the metabolic capacity is related to the fiber type composition of skeletal muscle under malnourished condition although malnutrition resulted in preferential atrophy in fast muscle. The purpose of the present study was to investigate the effects of metabolic capacity in fast and slow muscles via the energy-sensing of AMPK and SIRT1 in malnutrition. Wistar rats were randomly divided into control and malnutrition groups. The rats in the malnutrition group were provided with a low-protein diet, and daily food intake was limited to 50% for 12 weeks. Malnutrition with hypoalbuminemia decreased the body weight and induced the loss of plantaris muscle mass, but there was little change in the soleus muscle. An increase in the superoxide level in the plasma and a decrease in SOD-2 protein expression in both muscles were observed in the malnutrition group. In addition, the expression level of AMPK in the malnutrition group increased in both muscles. Conversely, the expression level of SIRT1 decreased in both muscles of the malnutrition group. In addition, malnutrition resulted in a decrease in the expression levels of PGC-1α and PINK protein, and induced a decrease in the levels of two key mitochondrial enzymes (succinate dehydrogenase and citrate synthase) and COX IV protein expression in both muscles. These results indicate that malnutrition impaired the metabolic capacity in both fast and slow muscles via AMPK-independent SIRT1 inhibition induced by increased oxidative stress.

Preventive effects of low-intensity endurance exercise for severe hyperglycemia-induced capillary regression in non-obese type 2 diabetes rat skeletal muscle.

Although endurance exercise is effective for reducing diabetes-related capillary regression, it is difficult to prescribe high-intensity endurance exercise due to the potential worsening of complications in patients with severe hyperglycemia. Therefore, this study aimed to examine whether chronic low-intensity exercise training may prevent severe hyperglycemia-induced capillary regression of skeletal muscle in non-obese type 2 diabetes. Non-diabetic Sprague Dawley rats were assigned to a control (Con) group and an exercise (Ex) group. Likewise, spontaneously diabetic Torii rats were assigned to a diabetic sedentary (DM) group or a diabetic exercise (DMEx) group. Rats in the Ex and DMEx groups were placed on a motor-driven treadmill running at low speed (15 m/min) for 60 min/day, 5 days/week, for 14 weeks. Serum glucose levels were significantly increased in the DM group, but not in the DMEx group. Although the capillary-to-fiber ratio in the plantaris muscle was significantly lower in the DM group compared to the control group, the ratio in the DMEx group was significantly higher compared to the DM group. Moreover, the succinate dehydrogenase activity and expression levels of vascular endothelial growth factor and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) were reduced in the plantaris muscle of the DM group. However, those in the DMEx group were significantly higher than those in the DM group. These results indicate that low-intensity chronic endurance exercise training has the potential to prevent the progression of capillary regression in the skeletal muscles of non-obese type 2 diabetes patients with severe hyperglycemia.