Prevent Muscle Atrophy Research Articles

The AKT Pathway and Satellite Cell Activation in Skeletal Muscle Mass Regulation

Highlight:AKT or protein kinase B increase protein synthesis and control the degradation of proteins. Satellite cells was provided remarkable ability to regenerate skeletal muscle.Stimulation of protein synthesis is effective therapy to maintain muscle mass, prevent muscle wasting to reduce risk sarcopenia and improve quality of life in the elderly.Abstract:Muscles have an important role as a regulator of glucose and triglyceride metabolism. Some researches show the correlation between skeletal muscle mass and metabolic diseases, such as diabetes. Skeletal muscle mass decrease occurs due to chronic illness or physiological process of aging, thus increasing the risk of metabolic diseases as well as motion difficulty in the elderly. Skeletal muscle mass depends on balanced protein synthesis and degradation, controlled through a variety of signal transduction pathways including the AKT. AKT or protein kinase B increases protein synthesis through the mTOR and GSK3β and controls the degradation of proteins through FoxO transcription factors. Another factor that has an alleged role in the regulation of skeletal muscle is the satellite cells which provide remarkable ability to regenerate skeletal muscle. A comprehensive understanding of the biomolecular mechanism of muscle mass regulation is important to develop effective treatment or prevention of muscle atrophy in many cases, either caused by pathological conditions, such as chronic diseases, or the process of aging.

Yeast hydrolysate ameliorates dexamethasone-induced muscle atrophy by suppressing MuRF-1 expression in C2C12 cells and C57BL/6 mice

• Effect of YH on C2C12 cell and DEX-induced muscle atrophy mouse were conducted. • YH can promote muscle differentiation in C2C12 cell. • YH prevented muscle atrophy via downregulating MuRF-1, FoxO3a, Atrogin-1 in vitro . • YH prevented skeletal muscle loss and downregulates MuRF-1 in DEX-induced muscle atrophy mouse model. In this study, we evaluated the effects of yeast ( Saccharomyces cerevisiae ) hydrolysate (YH) on muscle differentiation and muscle atrophy inhibitory activity in C2C12 cells and atrophy inhibitory activity in a dexamethasone (DEX)-induced muscle atrophy mouse model. Jenner-Giemsa staining revealed that the length and area of ​​myotubes increased in the YH groups. Moreover, the gene expression of myogenic differentiation 1 and myogenin was significantly increased in the YH groups. In the DEX-induced muscle atrophy C2C12 model, the expression of muscle ring-finger protein-1 (MuRF-1), forkhead box class O3a, and Atrogin-1 were significantly reduced in the YH groups. Furthermore, in the muscle-atrophy mice model, grip strength and lean mass were increased by 1.28-fold and 3.5%, respectively compared to the control in the YH group (300 mg/kg). These results were confirmed by the downregulation of MuRF-1 in muscle. In conclusion, YH promoted muscle cell differentiation and exhibited an inhibitory effect on DEX-induced muscle atrophy.

Nutrients against Glucocorticoid-Induced Muscle Atrophy.

Glucocorticoid excess is a critical factor contributing to muscle atrophy. Both endogenous and exogenous glucocorticoids negatively affect the preservation of muscle mass and function. To date, the most effective intervention to prevent muscle atrophy is to apply a mechanical load in the form of resistance exercise. However, glucocorticoid-induced skeletal muscle atrophy easily causes fatigue in daily physical activities, such as climbing stairs and walking at a brisk pace, and reduces body movements to cause a decreased ability to perform physical activity. Therefore, providing adequate nutrients in these circumstances is a key factor in limiting muscle wasting and improving muscle mass recovery. The present review will provide an up-to-date review of the effects of various nutrients, including amino acids such as branched-chain amino acids (BCAAs) and β–hydroxy β–methylbutyrate (HMB), fatty acids such as omega-3, and vitamins and their derivates on the prevention and improvement of glucocorticoid-induced muscle atrophy.

Myricanol Inhibits Platelet Derived Growth Factor-BB-Induced Vascular Smooth Muscle Cells Proliferation and Migration in vitro and Intimal Hyperplasia in vivo by Targeting the Platelet-Derived Growth Factor Receptor-β and NF-κB Signaling.

The abnormal proliferation and migration of Vascular smooth muscle cells (VSMCs) are related to many cardiovascular diseases, including atherosclerosis, restenosis after balloon angioplasty, hypertension, etc. Myricanol is a diarylheptanoid that can be separated from the bark of Myrica rubra. It has been reported that myricanol can anti-inflammatory, anti-cancer, anti-neurodegenerative, promote autophagic clearance of tau and prevent muscle atrophy. But its potential role in the cardiovascular field remains unknown. In this study, we investigated the effect of myricanol on the proliferation and migration of VSMCs in vitro and on the intimal hyperplasia in vivo. In vitro experiments, we found myricanol can inhibit the proliferation and migration of VSMCs induced by PDGF-BB. In terms of mechanism, the preincubation of myricanol can suppress the PDGF-BB induced phosphorylation of PDGFRβ and its downstream such as PLCγ1, Src, and MAPKs. In addition, NF-kB p65 translocation was also suppressed by myricanol. In vivo experiments, we found myricanol can suppress the intimal hyperplasia after wire ligation of the carotid artery in mice. These results may provide a new strategy for the prevention and treatment of coronary atherosclerosis and post-stent stenosis in the future.

Interleukin 37's role in promoting nerve repair and attenuating immune rejection of peripheral nerve xenografts in mice

BackgroundThe aim of the study was to explore the potential role of IL-37 in nerve repair and immune regulation in peripheral nerve xenograft hosts.MethodsRat nerve xenografts were transplanted into mouse recipients. Transplanted mice received an intraperitoneal injection of IL-37 on the day before transplantation, whereas control mice remained untreated. At postoperative 2, 4, 8, and 12 weeks, the effects of IL-37 were examined on motor function, tissue morphology, and regenerative ability of xenograft nerves. Levels of IL-17 and IL-22 in serum and spleen were measured at 3, 7, 14, and 28 days after nerve transplantation.ResultsAt 12 postoperative weeks, grafted nerves grew well in IL-37 treatment group, as documented by the recovery in function of sciatic nerves compared to untreated controls. In particular, IL-37-treated mice showed more complete neuromorphology, thicker myelin sheath, compact structure, and the increased number of myelinated nerve fibers in histological examination. The number of T helper (Th)17 (CD3 + CD4 + IL-17+) and Th22 (CD3 + CD4 + IL-22+) cells in the spleen was reduced in the IL-37-treated group, as well as serum IL-17 and IL-22 were decreased after IL-37 treatment compared with the untreated group.ConclusionsIL-37 attenuates immunomodulatory responses induced by xenografts, contributing to the recovery of nerve function and the prevention of muscle atrophy caused by nerve grafts.

TLR13 contributes to skeletal muscle atrophy by increasing insulin resistance in chronic kidney disease.

ObjectivesInsulin resistance in chronic kidney disease (CKD) stimulates muscle wasting, but the molecular processes behind the resistance are undetermined. However, inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia. Toll‐like receptors (TLRs) are known to regulate local innate immune responses, and microarray data have shown that Tlr13 is upregulated in the muscles of mice with CKD, but the relevance is unknown.Materials and MethodsWe performed in vitro experiments in C2C12 myotubes and constructed a CKD murine model using subtotal nephrectomy to conduct experiments in vivo.Results Tlr13 expression was stimulated in C2C12 myotubes treated with uremic serum. The expression of Tlr13 was also upregulated in the tibialis anterior muscles of mice with CKD. Tlr13 knockdown with siRNAs in skeletal muscle cells decreased insulin resistance despite the inclusion of uremic serum. This led to increased levels of p‐AKT and suppression of protein degradation. Using immunofluorescence staining and coimmunoprecipitation assay, we found that TLR13 recruits IRF3, which activates Irf3 expression, resulting in decreased AKT activity. Moreover, insulin resistance and proteolysis are re‐induced by Irf3 overexpression under Tlr13 deletion.ConclusionsOur results indicate that TLR13 is involved in CKD‐mediated insulin resistance in muscle. In catabolic conditions where insulin signaling is impaired, targeting TLR13 may improve insulin sensitivity and prevent muscle atrophy.

8-Prenylnaringenin tissue distribution and pharmacokinetics in mice and its binding to human serum albumin and cellular uptake in human embryonic kidney cells.

8‐Prenylnaringenin (8‐PN), a hop flavonoid, is a promising food substance with health benefits. Compared with nonprenylated naringenin, 8‐PN exhibits stronger estrogenic activity and prevents muscle atrophy. Moreover, 8‐PN prevents hot flushes and bone loss. Considering that prenylation reportedly improves the bioavailability of flavonoids, we compared the parameters related to the bioavailability [pharmacokinetics and tissue distribution in C57/BL6 mice, binding affinity to human serum albumin (HSA), and cellular uptake in HEK293 cells] of 8‐PN and its mother (non‐prenylated) compound naringenin. C57/BL6 mice were fed an 8‐PN or naringenin mixed diet for 22 days. The amount of 8‐PN (nmol/g tissue) in the kidneys (16.8 ± 9.20), liver (14.8 ± 2.58), muscles (3.33 ± 0.60), lungs (2.07 ± 0.68), pancreas (1.80 ± 0.38), heart (1.71 ± 0.27), spleen (1.36 ± 0.29), and brain (0.31 ± 0.09) was higher than that of naringenin. A pharmacokinetic study in mice demonstrated that the C max of 8‐PN (50 mg/kg body weight) was lower than that of naringenin; however, the plasma concentration of 8‐PN 8 h after ingestion was higher than that of naringenin. The binding affinity of 8‐PN to HSA and cellular uptake in HEK293 cells were higher than those of naringenin. 8‐PN bioavailability features assessed in mouse or human model experiments were obviously different from those of naringenin.

Реабілітація хворих з переломами дистального метаепіфіза променевої кістки

Переломи дистального метаепіфіза променевої кістки (ПДМЕПК, переломи променя в типовому місці) зустрічаються досить часто, особливо у людей похилого віку. Незадовільні результати лікування у пацієнтів віком понад 70 років відмічаються у 44 % випадків. Робота присвячена поліпшенню результатів лікування хворих із переломами дистального метаепіфіза променевої кістки. Реабілітаційне лікування включало мультимодальне знеболювання, диференційовано і обґрунтовано застосовану медикаментозну терапію, щадну репозицію із застосуванням запропонованого пристрою, ранню кінезитерапію, масаж і фізіотерапію. Функціональні результати реабілітації хворих із переломами ДМЕПК за шкалою DASH свідчили про її високу ефективність.

Effects of electrode size and placement on comfort and efficiency during low-intensity neuromuscular electrical stimulation of quadriceps, hamstrings and gluteal muscles

BackgroundNeuromuscular electrical stimulation (NMES) may prevent muscle atrophy, accelerate rehabilitation and enhance blood circulation. Yet, one major drawback is that patient compliance is impeded by the discomfort experienced. It is well-known that the size and placement of electrodes affect the comfort and effect during high-intensity NMES. However, during low-intensity NMES the effects of electrode size/placement are mostly unknown. Therefore, the purpose of this study was to investigate how electrode size and pragmatic placement affect comfort and effect of low-intensity NMES in the thigh and gluteal muscles.MethodsOn 15 healthy participants, NMES-intensity (mA) was increased until visible muscle contraction, applied with three electrode sizes (2 × 2 cm, 5 × 5 cm, 5 × 9 cm), in three different configurations on quadriceps and hamstrings (short-transverse (ST), long-transverse (LT), longitudinal (L)) and two configurations on gluteus maximus (short-longitudinal (SL) and long-longitudinal (LL)). Current–density (mA/cm2) required for contraction was calculated for each electrode size. Comfort was assessed with a numerical rating scale (NRS, 0–10). Significance was set to p < 0.05 and values were expressed as median (inter-quartile range).ResultsOn quadriceps the LT-placement exhibited significantly better comfort and lower current intensity than the ST- and L-placements. On hamstrings the L-placement resulted in the best comfort together with the lowest intensity. On gluteus maximus the LL-placement demonstrated better comfort and required less intensity than SL-placement. On all muscles, the 5 × 5 cm and 5 × 9 cm electrodes were significantly more comfortable and required less current–density for contraction than the 2 × 2 cm electrode.ConclusionDuring low-intensity NMES-treatment, an optimized electrode size and practical placement on each individual muscle of quadriceps, hamstrings and gluteals is crucial for comfort and intensity needed for muscle contraction.

The possible role of ursolic acid in Covid-19: A real game changer.

Ursolic acid (UA) is a pentacyclic terpenoid is usually found in the fruit peels and stem bark as secondary metabolites. UA has antiviral, antibacterial, and antiparasitic properties. UA has a wide spectrum of pharmacological activities against different infections. Because of the greatest antiviral and anti-inflammatory properties of UA, so it could be a plausible therapeutic herbal medicine in Covid-19 treatment. Covid-19 is a recent worldwide virulent disease pandemic due to severe acute respiratory coronavirus disease 2 (SARS-CoV-2). The pathogenesis of SARS-CoV-2 infection is related to the direct cytopathic effect and exaggerated immune response by which acute lung injury (ALI) and/or acute respiratory distress syndrome might be developed in critical cases. UA may inhibit main protease of SARS-CoV-2, and inhibits the interface flanked by SARS-CoV-2 viral proteins and its entry point commonly recognized as angiotensin converting enzyme 2 (ACE2). In addition, UA attenuates SARS-CoV-2-induced inflammatory reactions and oxidative stress.Therefore, UA could avert SARS-CoV-2 infection from causing ALI. This opinion proposed that UA might be a potential candidate therapy against Covid-19 and can mitigate post-Covid-19 complications such as lung fibrosis. In this regards, forthcoming studies are reasonable to substantiate the therapeutic role of UA in Covid-19. However, taken into account that Covid-19 is yet to be investigating for further evaluations, therefore, clinical trials are recommended regarding use and dose of UA in Covid-19 treatment, as well as secondary effects.

Carotenoid transporter CD36 expression depends on hypoxia-inducible factor-1α in mouse soleus muscles.

Dietary β-carotene induces muscle hypertrophy and prevents muscle atrophy in red slow-twitch soleus muscles, but not in white fast-twitch extensor digitorum longus (EDL) muscles and gastrocnemius muscles. However, it remains unclear why these beneficial effects of β-carotene are elicited in soleus muscles. To address this issue, we focused on carotenoid transporters in skeletal muscles. In mice, Cd36 mRNA levels were higher in red muscle than in white muscle. The siRNA-mediated knockdown of CD36 decreased β-carotene uptake in C2C12 myotubes. In soleus muscles, CD36 knockdown inhibited β-carotene-induced increase in muscle mass. Intravenous injection of the hypoxia marker pimonidazole produced more pimonidazole-bound proteins in soleus muscles than in EDL muscles, and the hypoxia-inducible factor-1 (HIF-1) α protein level was higher in soleus muscles than in EDL muscles. In C2C12 myotubes, hypoxia increased the expression of CD36 and HIF-1α at the protein and mRNA levels, and HIF-1α knockdown reduced hypoxia-induced increase in Cd36 mRNA level. In soleus muscles, HIF-1α knockdown reduced Cd36 mRNA level. These results indicate that CD36 is predominantly involved in β-carotene-induced increase in soleus muscle mass of mice. Furthermore, we demonstrate that CD36 expression depends on HIF-1α in the soleus muscles of mice, even under normal physiological conditions.

The Role of Branched Chain Amino Acids for Heart Failure in Children

Heart failure is an abnormality of the heart’s structure or function, causing impairment in oxygen delivery to peripheral tissue. The most common causes of heart failure in children are congenital heart disease and cardiomyopathies. Impairment in cardiac function will affect nutritional status such as higher metabolic demands, lower intake, nutrients malabsorption, and failure to thrive. About 86% children with chronic heart failure had malnutrition. Branched chain amino acids (BCAAs) are essential amino acids that involved in protein synthesis, muscle atrophy prevention, and regulating biogenesis of mitochondrial for cardiac energy formation. This review elucidates current findings on BCAAs supplementation for children with heart failure.

Overexpression of thioredoxin‐2 attenuates age‐related muscle loss by suppressing mitochondrial oxidative stress and apoptosis

AbstractBackgroundSkeletal muscle mass is regulated by intracellular anabolic and catabolic activities. Increased catabolic activity can shift the balance towards net protein breakdown and muscle atrophy. Mitochondrial oxidative stress activates catabolism and is linked to muscle loss. Reducing mitochondrial oxidative stress is thus a plausible approach to prevent muscle atrophy. We tested this concept in age‐dependent muscle atrophy by genetically overexpressing the mitochondrial antioxidant thioredoxin‐2 (TXN2).MethodsWe tested the functional role of TXN2 using ageing (n = 7–10 per group) and denervation (n = 3 per group) models in a transgenic mouse line that overexpresses TXN2. We investigated if overexpression of TXN2 blocks muscle loss in these models by examination of muscle weight, fibre size, and fibre number in young (~7 months) and aged (~26 months) TXN2‐transgenic mice and controls. We studied the underlying mechanisms by mRNA and protein assays including transcriptomic profiling, western blot analysis, immunostaining, as well as succinate dehydrogenase, dihydroethidium, and terminal deoxynucleotidyl transferase dUTP nick end labelling staining.ResultsOverexpression of TXN2 did not significantly alter the baseline skeletal muscle size, weight, fibre type distribution, or expression of mitochondrial respiratory chain components, but it did preserve muscle mass during ageing. The hindlimb muscle mass in aged TXN‐transgenic mice was ~21–24% greater (in tibialis anterior, gastrocnemius/soleus combined, and tibialis anterior/extensor digitorum longus combined) than in age‐matched controls (all P &lt; 0.05). The reduction in both muscle fibre number (872 ± 206 vs, 637 ± 256 fibres in extensor digitorum longus muscle, P &lt; 0.05) and muscle fibre size (1959 ± 296 vs. 1477 ± 564 μm2 in tibialis anterior muscle, P &lt; 0.05) seen in young vs. aged control muscles was not significant in young vs. aged TXN‐transgenic mice (both P &gt; 0.05). Transcriptomic analysis revealed that catabolic genes that are up‐regulated in ageing muscle, including those subserving apoptosis and the ubiquitin‐like conjugation system, were normalized by TXN2 overexpression. Further, overexpressing TXN2 suppressed oxidative stress and caspase‐9/3‐mediated apoptotic signalling in the aged muscle at the protein level. Although denervation and its effects have been considered a component of age‐related muscle atrophy, TXN2 overexpression failed to attenuate atrophy in an acute denervation model (TXN‐transgenic vs. control mice, P &gt; 0.05), despite preventing denervation‐induced oxidative stress and apoptosis.ConclusionsMitochondrial oxidative stress appears to play a crucial role in effecting chronic age‐dependent, but not acute neurogenic, muscle atrophy. Increased TXN2 protects muscle against oxidative stress‐associated catabolic activity in ageing muscle and thus is a potential therapeutic approach to attenuate age‐related muscle atrophy.

Effects of Low-Load Blood-Flow Restricted Resistance Training on Functional Capacity and Patient-Reported Outcome in a Young Male Suffering From Reactive Arthritis.

Introduction: Reactive arthritis (ReA) is a chronic inflammatory disease usually caused by a preceding gastrointestinal or genitourinary bacterial infection. ReA usually occurs in the lower limbs causing joint pain and joint swelling. Physiotherapy-led exercise is recommended to prevent muscle atrophy. The purpose of this case report is to describe the outcome after 12 weeks of low-load blood flow restricted resistance training (BFR-RT) as a rehabilitation method for a young male suffering from ReA.Methods and materials: A 17-year-old male suffered from ReA in the both knee joints and the left hip joint. 36 months after the incident, he suffered from another ReA incident in his right knee. Non-steroid anti-inflammatory drugs and a new arthrocentesis added with corticosteroid injection was unsuccessful in treating the ReA. The patient performed 12 weeks of BFR-RT on the right lower limb with a low amount of supervision after the first week of training. Assessment of unilateral 30-sec chair stand test (u30-sec CST), low-thigh circumference above apex patella, The Knee Injury and Osteoarthritis Outcome Score (KOOS), The Forgotten Knee Joint Score (FJS), and Numeric Ranking Scale for pain (NRS) was performed at baseline and after 3,6,9, and 12 weeks of BFR-RT.Results: The patient completed all planned exercise sessions. u30-sec CST improved with 7 repetitions (reps) on the right limb and 5 reps on the left leg. Low-thigh circumference decreased 1.1 cm on the right leg and 1.0 on the left leg. KOOS symptoms, ADL, quality of life and FJS demonstrated a clinically relevant change on 10, 14 and 23 points.Conclusion: The present case study indicates that even with low amounts of supervision BFR-RT could increase functional performance, reduce knee joint swelling and improve key patient-reported outcome.

Phytochemical‑rich herbal formula ATG‑125 protects against sucrose‑induced gastrocnemius muscle atrophy by rescuing Akt signaling and improving mitochondrial dysfunction in young adult mice.

The antioxidant capability of herbal remedies has attracted widespread attention, but their molecular mechanisms in a muscle atrophy model have not been explored. The aim of the present study was to compare the bioactivity of sucrose challenged mice following treatment with ATG-125. Here, through a combination of transcriptomic and biomedical analysis, herbal formula ATG-125, a phytochemical-rich formula, was identified as a protective factor against muscle atrophy in sucrose challenged mice. Gene ontology (GO) identified differentially expressed genes that were primarily enriched in the ‘negative regulation of proteolysis’, ‘cellular amino acid metabolic process’, ‘lipoprotein particle’ and ‘cell cycle’, all of which were associated with the ATG-125-mediated prevention of muscle atrophy, particularly with regard to mitochondrial biogenesis. In skeletal muscle, a set of mitochondrial-related genes, including angiopoietin-like 4, nicotinamide riboside kinase 2 (Nmrk2), pyruvate dehydrogenase lipoamide kinase isozyme 4, Asc-type amino acid transporter 1 and mitochondrial uncoupling protein 3 (Ucp3) were markedly upregulated following ATG-125 intervention. An increase in Nmrk2 and Ucp3 expression were noted after ATG-125 treatment, in parallel with upregulation of the ‘nicotinate and nicotinamide metabolism’ pathway, as determined using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Furthermore, KEGG pathway analysis revealed the downregulation of ‘complement and coagulation cascades’, ‘cholesterol metabolism’, ‘biosynthesis of amino acids’ and ‘PPAR signaling pathway’, which were associated with the downregulation of serine (or cysteine) peptidase inhibitor clade A member (Serpina)3, Serpina1b, Serpina1d, Serpina1e, apolipoprotein (Apo)a1 and Apoa2, all of which were cardiovascular and diabetes-associated risk factors and were regulated by ATG-125. In addition, ATG-125 treatment resulted in downregulated mRNA expression levels of ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2, troponin-I1, troponin-C1 and troponin-T1 in young adult gastrocnemius muscle compared with the sucrose group. Nuclear factor-κB-hypoxia inducible factor-1α-TGFβ receptor type-II-vascular endothelial growth factor staining indicated that ATG-125 decreased sucrose-induced chronic inflammation. ATG-125 was sufficient to prevent muscle atrophy, and this protective effect may be mediated through upregulation of AKT phosphorylation, upregulating the insulin growth factor-1R-insulin receptor substrate-PI3K-AKT pathway, which in turn resulted in a forkhead box O-dependent decrease in protein degradation pathways, including regulation of atrogin1 and E3 ubiquitin-protein ligase TRIM63. Peroxisome-proliferator activated receptor γ coactivator 1α (PGC1α) was decreased in young adult mice challenged with sucrose. ATG-125 treatment significantly increased PGC1α and significantly increased UCP-1,2,3 expression levels, which suggested ATG-125 poised the mitochondria for uncoupling of respiration. This effect is consistent with the increased SIRT1 levels and may explain an increase in mitochondria biogenesis. Taken together, the present study showed that ATG-125, as an integrator of protein synthesis and degradative pathways, prevented muscle wasting.

Hypoglycemic effects of Fu-Pen-Zi (Rubus chingii Hu) fruit extracts in streptozotocin-induced type 1 diabetic mice

• FPZ alleviated hyperglycemia in STZ-induced diabetic mice. • FPZ increased antioxidant response and protected pancreatic islet against STZ-induced damage. • FPZ inhibited Atrogin-1 and Trim63 expression and prevented muscle atrophy. To explore the effects of Chinese raspberry (Fu-Pen-Zi) on diabetes, a polyphenol-enriched extract (FPZ) was prepared. Streptozotocin (STZ)-induced diabetic mice were daily administered FPZ (30 mg/kg body weight) for 18 days, the anti-diabetic effects were evaluated. Compared to STZ alone mice, FPZ-treatment ameliorated STZ-induced type 1 diabetes, reduced body weight loss (by 71.61%), hyperglycemia (fasting blood glucose reduced by 19.23%), hyperlipidemia (hepatic triglycerides reduced by 15.50%) and skeletal muscle atrophy (quadriceps mass increased by 21.46%). FPZ protected pancreatic β-cells from STZ-induced damage and promoted insulin secretion, preserved insulin signaling in liver tissues and skeletal muscles. FPZ improved glucose tolerance, modulated liver glycogen metabolism, and inhibited hepatic gluconeogenesis via activating insulin/Akt/Gsk3β and LKB1/AMPK signaling. Moreover, FPZ reduced liver oxidative stress and steatosis, reduced Atrogin-1 and Trim63 expression, contributes to muscle atrophy inhibition. This study highlights the potential usage of FPZ as nutritional interventions for type 1 diabetes and muscle atrophy management.

The effect of passive mobilization associated with blood flow restriction and combined with electrical stimulation on cardiorespiratory safety, neuromuscular adaptations, physical function, and quality of life in comatose patients in an ICU: a randomized controlled clinical trial

BackgroundIntensive care unit-acquired atrophy and weakness are associated with high mortality, a reduction in physical function, and quality of life. Passive mobilization (PM) and neuromuscular electrical stimulation were applied in comatose patients; however, evidence is inconclusive regarding atrophy and weakness prevention. Blood flow restriction (BFR) associated with PM (BFRp) or with electrical stimulation (BFRpE) was able to reduce atrophy and increase muscle mass in spinal cord-injured patients, respectively. Bulky venous return occurs after releasing BFR, which can cause unknown repercussions on the cardiovascular system. Hence, the aim of this study was to investigate the effect of BFRp and BFRpE on cardiovascular safety and applicability, neuromuscular adaptations, physical function, and quality of life in comatose patients in intensive care units (ICUs).MethodsThirty-nine patients will be assessed at baseline (T0–18 h of coma) and randomly assigned to the PM (control group), BFRp, or BFRpE groups. The training protocol will be applied in both legs alternately, twice a day with a 4-h interval until coma awake, death, or ICU discharge. Cardiovascular safety and applicability will be evaluated at the first training session (T1). At T0 and 12 h after the last session (T2), muscle thickness and quality will be assessed. Global muscle strength and physical function will be assessed 12 h after T2 and ICU and hospital discharge for those who wake up from coma. Six and 12 months after hospital discharge, physical function and quality of life will be re-assessed.DiscussionIn view of applicability, the data will be used to inform the design and sample size of a prospective trial to clarify the effect of BFRpE on preventing muscle atrophy and weakness and to exert the greatest beneficial effects on physical function and quality of life compared to BFRp in comatose patients in the ICU.Trial registrationUniversal Trial Number (UTN) Registry UTN U1111-1241-4344. Retrospectively registered on 2 October 2019. Brazilian Clinical Trials Registry (ReBec) RBR-2qpyxf. Retrospectively registered on 21 January 2020, http://ensaiosclinicos.gov.br/rg/RBR-2qpyxf/

Aerobic exercise and resistance exercise alleviate skeletal muscle atrophy through IGF-1/IGF-1R-PI3K/Akt pathway in mice with myocardial infarction.

Myocardial infarction (MI)-induced heart failure (HF) is commonly accompanied with profound effects on skeletal muscle. With the process of MI-induced HF, perturbations in skeletal muscle contribute to muscle atrophy. Exercise is viewed as a feasible strategy to prevent muscle atrophy. The aims of this study were to investigate whether exercise could alleviate MI-induced skeletal muscle atrophy via insulin-like growth factor 1 (IGF-1) pathway in mice. Male C57/BL6 mice were used to establish the MI model and were divided into three groups: sedentary MI group (MI), MI with aerobic exercise group, and MI with resistance exercise group; sham-operated group was used as control. Exercise-trained animals were subjected to 4 wk of aerobic exercise (AE) or resistance exercise (RE). Cardiac function, muscle weight, myofiber size, levels of IGF-1 signaling and proteins related to myogenesis, protein synthesis, and degradation and apoptosis in gastrocnemius muscle were detected. H2O2-treated C2C12 cells were intervened with recombinant human IGF-1, IGF-1 receptor (IGF-1R) inhibitor NVP-AEW541, and PI3K inhibitor LY294002 to explore the mechanism. Exercises upregulated the IGF-1/IGF-1R-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling; increased the expressions of Pax7, myogenic regulatory factors (MRFs), and protein synthesis; and reduced protein degradation and cell apoptosis in MI mice. In vitro, IGF-1 upregulated the levels of Pax7, MRFs, mTOR, and P70S6K; reduced MuRF1 and MAFbx; and inhibited cell apoptosis via IGF-1R-PI3K/Akt pathway. AE and RE, safely and effectively, alleviate skeletal muscle atrophy by regulating the levels of myogenesis, protein degradation, and cell apoptosis in mice with MI via activating IGF-1/IGF-1R-PI3K/Akt signaling pathway.

Leucine-Rich Diet Improved Muscle Function in Cachectic Walker 256 Tumour-Bearing Wistar Rats.

Skeletal muscle atrophy occurs in several pathological conditions, such as cancer, especially during cancer-induced cachexia. This condition is associated with increased morbidity and poor treatment response, decreased quality of life, and increased mortality in cancer patients. A leucine-rich diet could be used as a coadjutant therapy to prevent muscle atrophy in patients suffering from cancer cachexia. Besides muscle atrophy, muscle function loss is even more important to patient quality of life. Therefore, this study aimed to investigate the potential beneficial effects of leucine supplementation on whole-body functional/movement properties, as well as some markers of muscle breakdown and inflammatory status. Adult Wistar rats were randomly distributed into four experimental groups. Two groups were fed with a control diet (18% protein): Control (C) and Walker 256 tumour-bearing (W), and two other groups were fed with a leucine-rich diet (18% protein + 3% leucine): Leucine Control (L) and Leucine Walker 256 tumour-bearing (LW). A functional analysis (walking, behaviour, and strength tests) was performed before and after tumour inoculation. Cachexia parameters such as body weight loss, muscle and fat mass, pro-inflammatory cytokine profile, and molecular and morphological aspects of skeletal muscle were also determined. As expected, Walker 256 tumour growth led to muscle function decline, cachexia manifestation symptoms, muscle fibre cross-section area reduction, and classical muscle protein degradation pathway activation, with upregulation of FoxO1, MuRF-1, and 20S proteins. On the other hand, despite having no effect on the walking test, inflammation status or muscle oxidative capacity, the leucine-rich diet improved muscle strength and behaviour performance, maintained body weight, fat and muscle mass and decreased some protein degradation markers in Walker 256 tumour-bearing rats. Indeed, a leucine-rich diet alone could not completely revert cachexia but could potentially diminish muscle protein degradation, leading to better muscle functional performance in cancer cachexia.

Molecular and Metabolic Mechanism of Low-Intensity Pulsed Ultrasound Improving Muscle Atrophy in Hindlimb Unloading Rats.

Low-intensity pulsed ultrasound (LIPUS) has been proved to promote the proliferation of myoblast C2C12. However, whether LIPUS can effectively prevent muscle atrophy has not been clarified, and if so, what is the possible mechanism. The aim of this study is to evaluate the effects of LIPUS on muscle atrophy in hindlimb unloading rats, and explore the mechanisms. The rats were randomly divided into four groups: normal control group (NC), hindlimb unloading group (UL), hindlimb unloading plus 30 mW/cm2 LIPUS irradiation group (UL + 30 mW/cm2), hindlimb unloading plus 80 mW/cm2 LIPUS irradiation group (UL + 80 mW/cm2). The tails of rats in hindlimb unloading group were suspended for 28 days. The rats in the LIPUS treated group were simultaneously irradiated with LIPUS on gastrocnemius muscle in both lower legs at the sound intensity of 30 mW/cm2 or 80 mW/cm2 for 20 min/d for 28 days. C2C12 cells were exposed to LIPUS at 30 or 80 mW/cm2 for 5 days. The results showed that LIPUS significantly promoted the proliferation and differentiation of myoblast C2C12, and prevented the decrease of cross-sectional area of muscle fiber and gastrocnemius mass in hindlimb unloading rats. LIPUS also significantly down regulated the expression of MSTN and its receptors ActRIIB, and up-regulated the expression of Akt and mTOR in gastrocnemius muscle of hindlimb unloading rats. In addition, three metabolic pathways (phenylalanine, tyrosine and tryptophan biosynthesis; alanine, aspartate and glutamate metabolism; glycine, serine and threonine metabolism) were selected as important metabolic pathways for hindlimb unloading effect. However, LIPUS promoted the stability of alanine, aspartate and glutamate metabolism pathway. These results suggest that the key mechanism of LIPUS in preventing muscle atrophy induced by hindlimb unloading may be related to promoting protein synthesis through MSTN/Akt/mTOR signaling pathway and stabilizing alanine, aspartate and glutamate metabolism.