Decrease In Muscle Protein Synthesis Research Articles

Consuming Whey Protein with Added Essential Amino Acids, not Carbohydrate, Maintains Post-Exercise Anabolism while Underfed.

Energy deficiency decreases muscle protein synthesis (MPS), possibly due to greater whole-body essential amino acid (EAA) requirements and reliance on energy stores. Whether energy deficit-induced anabolic resistance is overcome with non-nitrogenous supplemental energy or if increased energy as EAA is needed is unclear. We tested the effects of energy as EAA or carbohydrate, combined with an EAA-enriched whey protein, on post-exercise MPS (%/h) and whole-body protein turnover (g protein/240 min). 17 adults (mean ± SD; age: 26 ± 6 y, BMI: 25 ± 3 kg/m2) completed a randomized, parallel study including two 5-d energy conditions (BAL, energy balance; DEF, -30 ± 3% energy requirements) separated by ≥7 d. Volunteers consumed EAA-enriched whey with added EAA (+EAA; 304 kcal, 56 g protein, 48 g EAA, 17 g carbohydrate, 2 g fat; n = 8) or added carbohydrate (+CHO; 311 kcal, 34 g protein, 24 g EAA, 40 g carbohydrate, 2 g fat; n = 9) following exercise. MPS and whole-body protein synthesis (PS), breakdown (PB), and net balance (NET; PS-PB) were estimated postexercise with isotope kinetics. MPS rates were greater in +EAA (0.083 ± 0.02) than +CHO (0.059 ± 0.01; P = 0.015) during DEF, but similar during BAL (P = 0.45) and across energy conditions within treatments (P = 0.056). PS rates were greater for +EAA (BAL, 117.9 ± 16.5; DEF, 110.3 ± 14.8) than +CHO (BAL, 81.6 ± 8.0; DEF, 83.8 ± 5.9 g protein/240 min; both P < 0.001), and greater during BAL than DEF in +EAA (P = 0.045). PB rates were less in +EAA (8.0 ± 16.5) than +CHO (37.8 ± 7.6 g protein/240 min; P < 0.001), and NET was greater in +EAA (106.1 ± 6.3) than +CHO (44.8 ± 8.5 g protein/240 min; P < 0.001). These data suggest that supplementing EAA-enriched whey protein with more energy as EAA, not carbohydrate, maintains postexercise MPS during energy deficit at rates comparable to those observed during energy balance.

FGF21 Induces Skeletal Muscle Atrophy and Increases Amino Acids in Female Mice: A Potential Role for Glucocorticoids.

Fibroblast growth factor-21 (FGF21) is an intercellular signaling molecule secreted by metabolic organs, including skeletal muscle, in response to intracellular stress. FGF21 crosses the blood-brain barrier and acts via the nervous system to coordinate aspects of the adaptive starvation response, including increased lipolysis, gluconeogenesis, fatty acid oxidation, and activation of the hypothalamic-pituitary-adrenocortical (HPA) axis. Given its beneficial effects for hepatic lipid metabolism, pharmaceutical FGF21 analogues are used in clinical trials treatment of fatty liver disease. We predicted pharmacologic treatment with FGF21 increases HPA axis activity and skeletal muscle glucocorticoid signaling and induces skeletal muscle atrophy in mice. Here we found a short course of systemic FGF21 treatment decreased muscle protein synthesis and reduced tibialis anterior weight; this was driven primarily by its effect in female mice. Similarly, intracerebroventricular FGF21 reduced tibialis anterior muscle fiber cross-sectional area; this was more apparent among female mice than male littermates. In agreement with the reduced muscle mass, the topmost enriched metabolic pathways in plasma collected from FGF21-treated females were related to amino acid metabolism, and the relative abundance of plasma proteinogenic amino acids was increased up to 3-fold. FGF21 treatment increased hypothalamic Crh mRNA, plasma corticosterone, and adrenal weight, and increased expression of glucocorticoid receptor target genes known to reduce muscle protein synthesis and/or promote degradation. Given the proposed use of FGF21 analogues for the treatment of metabolic disease, the study is both physiologically relevant and may have important clinical implications.

Popular Dietary Trends' Impact on Athletic Performance: A Critical Analysis Review.

Nutrition fuels optimal performance for athletes. With increased research developments, numerous diets available, and publicity from professional athletes, a review of dietary patterns impact on athletic performance is warranted. The Mediterranean diet is a low inflammatory diet linked to improved power and muscle endurance and body composition. Ketogenic diets are restrictive of carbohydrates and proteins. Though both show no decrements in weight loss, ketogenic diets, which is a more restrictive form of low-carbohydrate diets, can be more difficult to follow. High-protein and protein-paced versions of low-carbohydrate diets have also shown to benefit athletic performance. Plant-based diets have many variations. Vegans are at risk of micronutrient deficiencies and decreased leucine content, and therefore, decreased muscle protein synthesis. However, the literature has not shown decreases in performance compared to omnivores. Intermittent fasting has many different versions, which may not suit those with comorbidities or specific needs as well as lead to decreases in sprint speed and worsening time to exhaustion. This paper critically evaluates the research on diets in relation to athletic performance and details some of the potential risks that should be monitored. No one diet is universally recommend for athletes; however, this article provides the information for athletes to analyze, in conjunction with medical professional counsel, their own diet and consider sustainable changes that can help achieve performance and body habitus goals.

Impact of ergot alkaloid and steroidal implant on whole-body protein turnover and expression of mTOR pathway proteins in muscle of cattle.

Holstein steers (n = 32) were used to determine if the ergot analog, bromocriptine decreases muscle protein synthesis through inhibitory action on the mTOR pathway via a direct effect on signal proteins, and if these negative effects can be alleviated with anabolic agents. Steers were treated with intramuscular administration of bromocriptine (vehicle or 0.1 mg/kg BW) and a subdermal commercial steroidal implant containing trenbolone acetate (TBA) and estradiol 17β (with or without), in a 2×2 factorial design. During the 35 day experiment, intake was restricted to 1.5 times maintenance energy requirement. On days 27 through 32, steers were moved to metabolism stalls for urine collection, and whole-body protein turnover was determined using a single pulse dose of [15N] glycine into the jugular vein on day 28. On day 35, skeletal muscle samples were collected before (basal state) and 60 min after (stimulated state) an i.v. glucose challenge (0.25 g glucose/kg). Blood samples were collected at regular intervals before and after glucose infusion for determination of circulating concentrations of glucose and insulin. Bromocriptine reduced insulin and glucose clearance following the glucose challenge, indicating decreased insulin sensitivity and possible disruption of glucose uptake and metabolism in the skeletal muscle. Conversely, analysis of whole-body protein turnover demonstrated that bromocriptine does not appear to affect protein synthesis or urea excretion. Western immunoblot analysis of skeletal muscle showed that it did not affect abundance of S6K1 or 4E-BP1, so bromocriptine does not appear to inhibit activation of the mTOR pathway or protein synthesis. Estradiol/TBA implant decreased urea excretion and protein turnover but had no effect on protein synthesis, suggesting that steroidal implants promote protein accretion through unchanged rates of synthesis and decreased degradation, even in the presence of bromocriptine, resulting in improved daily gains. Implanted steers likely experienced increased IGF-1 signaling, but downstream activation of mTOR, S6K and 4E-BP1, and thus increased protein synthesis did not occur as expected. Overall, this data suggests that bromocriptine does not have a negative impact on muscle protein synthetic pathways independent of DMI.

High Protein Diet Has Beneficial Effects in Murine Muscular Dystrophy

In normal muscle there is a delicate balance between muscle protein synthesis and protein degradation. It is believed that this balance is disturbed in muscular dystrophy (MD) by decreased muscle protein synthesis and/or increased muscle protein degradation, resulting in net catabolism. In an attempt to reduce or reverse this catabolism, a high protein diet (HPD, 50% protein) was fed to dystrophic mice (129/ReJ dy) for 4 wk. The effects on muscle biochemistry, muscle function and muscle morphology were compared with those in dystrophic mice fed a normal diet (NPD, 20% protein) and in nondystrophic mice (NORM) also fed the 20% protein diet. Compared with NORM mice, NPD mice demonstrated greater rates of muscle protein synthesis (P < 0.05) as measured by the incorporation of labeled phenylalanine into muscle, greater protein degradation (P < 0.01) as measured by urinary 3-methylhistidine excretion, and lower muscle protein concentration (P < 0.01). When dystrophic mice were fed HPD for 4 wk, protein degradation was lower (P < 0.01) and muscle protein concentration greater (P < 0.01) than in NPD mice. These biochemical improvements were accompanied by greater morphological uniformity of muscle fibers, higher volume density of muscle fibers per unit area of muscle (P < 0.01), and lower shape factor (P < 0.01). Functionally, HPD led to improved muscle endurance (P < 0.01) and increased hind-limb utilization (P 0.01). We conclude that in murine dystrophy, HPD decreases net muscle catabolism, principally by decreasing muscle protein degradation, resulting in improvement in muscle morphology, strength and function.

Lespedeza bicolor extract supplementation reduced hyperglycemia-induced skeletal muscle damage by regulation of AMPK/SIRT/PGC1α–related energy metabolism in type 2 diabetic mice

Lespedeza bicolor (LB) is known to have antidiabetic activities; however, the underlying molecular mechanisms of LB in hyperglycemia-induced skeletal muscle damage is unclear. Inflammation and oxidative stress caused by type 2 diabetes mellitus (T2DM) not only contributes to insulin resistance, but also promotes muscle atrophy via decreased muscle protein synthesis and increased protein degradation, leading to frailty and sarcopenia. In this study, we hypothesized that LB extract (LBE) supplementatin has an ameliorative effect on hyperglycemia-induced skeletal muscle damage by activation of 5′ adenosine monophosphate-activated protein kinase (AMPK)/sirtuin (SIRT)/proliferator-activated receptor γ coactivator 1α (PGC1α)–associated energy metabolism in mice with T2DM. Diabetes was induced by a high-fat diet with a 2-time streptozotoxin injection (30 mg/kg body weight) in male C57BL/6J mice. After diabetes was induced (fasting blood glucose level ≥140 mg/dL), the mice were administered with LBE at a low dose (100 mg/kg/d) or high dose (250 mg/kg/d) by gavage for 12 weeks. LBE supplementation ameliorated glucose tolerance and hemoglobin A1c (%) in mice with T2DM. Moreover, LBE supplementation upregulated protein levels of insulin receptor subunit-1 and Akt accompanied by increased translocation of glucose transporter 4 in mice with T2DM. Furthermore, LBE increased mitochondrial biogenesis by activating SIRT1, SIRT3, SIRT4, and peroxisome PGC1α in diabetic skeletal muscle. Meanwhile, LBE supplementation reduced oxidative stress and inflammation in mice with T2DM. Taken together, the current study suggested that LBE could be a potential therapeutic to prevent skeletal muscle damage by regulation AMPK/SIRT/PGC1α–related energy metabolism in T2DM.

Resistance exercise and nutritional interventions for augmenting sarcopenia outcomes in chronic kidney disease: a narrative review.

Sarcopenia is an age‐related progressive muscle disease characterized by loss of muscle mass, muscle strength and physical performance with high prevalence in chronic kidney disease (CKD). CKD is associated with decreased muscle protein synthesis and muscle breakdown due to a number of factors including, the uremic inflammatory environment of the disease. CKD patients are highly sedentary and at risk of malnutrition which may exacerbate sarcopenia outcomes even further. Short and long‐term exercise and nutritional interventions have been studied and found to have some positive effects on sarcopenia measures in CKD. This narrative review summarized evidence between 2010 and 2020 of resistance exercise (RE) alone or combined with nutritional interventions for improving sarcopenia outcomes in CKD. Due to lack of CKD‐specific sarcopenia measures, the second European Working Group on Sarcopenia in Older People (EWGSOP2) definition has been used to guide the selection of the studies. The literature search identified 14 resistance exercise‐based studies and 5 nutrition plus RE interventional studies. Muscle strength outcomes were increased with longer intervention duration, intervention supervision, and high participant adherence. Data also suggested that CKD patients may require increased RE intensity and progressive loading to obtain detectable results in muscle mass. Unlike muscle strength and muscle mass, physical performance was readily improved by all types of exercise in long or short‐term interventions. Four studies used RE with high‐protein nutritional supplementation. These showed significant benefits on muscle strength and physical performance in dialysis patients while non‐significant results were found in muscle mass. More research is needed to confirm if a combination of RE and vitamin D supplementation could act synergistically to improve muscle strength in CKD. The current evidence on progressive RE for sarcopenia in CKD is encouraging; however, real‐life applications in clinical settings are still very limited. A multidisciplinary patient‐centred approach with regular follow‐up may be most beneficial due to the complexity of sarcopenia in CKD. Long‐term randomized control trials are needed to verify optimal RE prescription and explore safety and efficacy of other nutritional interventions in CKD.

Temporal changes in the markers of ribosome biogenesis in rat soleus muscle under simulated microgravity

Skeletal muscle inactivity due to real or simulated microgravity results in a significant atrophy of muscle fibers. One of the key causes of disuse atrophy is a decrease in the rate of muscle protein synthesis (MPS). MPS is dependent not only on translational efficiency but also on the number of ribosomes available for translation (translational capacity), however a time course for biomarkers of ribosome biogenesis during muscle disuse remains understudied. The aim of the study was to analyze temporal changes in the regulators/markers of ribosome biogenesis in rat soleus muscle during the course of disuse. Rats were subjected to hindlimb unloading (HU) for 1, 3, 7 and 14 days. 18S + 28S rRNA content was assessed by gel-electrophoresis; expression levels of 45S pre-rRNA and c-Myc were determined by RT-PCR and the rate of MPS was measured using SUnSET method. The content of 18S + 28S rRNA and total RNA as well as 45S pre-rRNA expression significantly decreased after 1-day HU and remained diminished for the entire unloading period. c-Myc mRNA expression was downregulated following 1, 3 and 7 days of HU, but did not significantly differ from control after 14-day HU. MPS showed a progressive decrease from the 3rd to 14th day of HU. Thus, a decrease in MPS in rat soleus during 3-, 7- and 14-day HU was accompanied by downregulation of the key markers of translational capacity.

Advances in the Role of Leucine-Sensing in the Regulation of Protein Synthesis in Aging Skeletal Muscle.

Skeletal muscle anabolic resistance (i.e., the decrease in muscle protein synthesis (MPS) in response to anabolic stimuli such as amino acids and exercise) has been identified as a major cause of age-related sarcopenia, to which blunted nutrition-sensing contributes. In recent years, it has been suggested that a leucine sensor may function as a rate-limiting factor in skeletal MPS via small-molecule GTPase. Leucine-sensing and response may therefore have important therapeutic potential in the steady regulation of protein metabolism in aging skeletal muscle. This paper systematically summarizes the three critical processes involved in the leucine-sensing and response process: (1) How the coincidence detector mammalian target of rapamycin complex 1 localizes on the surface of lysosome and how its crucial upstream regulators Rheb and RagB/RagD interact to modulate the leucine response; (2) how complexes such as Ragulator, GATOR, FLCN, and TSC control the nucleotide loading state of Rheb and RagB/RagD to modulate their functional activity; and (3) how the identified leucine sensor leucyl-tRNA synthetase (LARS) and stress response protein 2 (Sestrin2) participate in the leucine-sensing process and the activation of RagB/RagD. Finally, we discuss the potential mechanistic role of exercise and its interactions with leucine-sensing and anabolic responses.

Sarcopenia in chronic liver disease: mechanisms and countermeasures.

Sarcopenia, a condition of low muscle mass, quality, and strength, is commonly found in patients with cirrhosis and is associated with adverse clinical outcomes including reduction in quality of life, increased mortality, and posttransplant complications. In chronic liver disease (CLD), sarcopenia is most commonly defined through the measurement of the skeletal muscle index of the third lumbar spine. A major contributor to sarcopenia in CLD is the imbalance in muscle protein turnover, which likely occurs due to a decrease in muscle protein synthesis and an elevation in muscle protein breakdown. This imbalance is assumed to arise due to several factors including accelerated starvation, hyperammonemia, amino acid deprivation, chronic inflammation, excessive alcohol intake, and physical inactivity. In particular, hyperammonemia is a key mediator of the liver-gut axis and is known to contribute to mitochondrial dysfunction and an increase in myostatin expression. Currently, the use of nutritional interventions such as late-evening snacks, branched-chain amino acid supplementation, and physical activity have been proposed to help the management and treatment of sarcopenia. However, little evidence exists to comprehensively support their use in clinical settings. Several new pharmacological strategies, including myostatin inhibition and the nutraceutical Urolithin A, have recently been proposed to treat age-related sarcopenia and may also be of use in CLD. This review highlights the potential molecular mechanisms contributing to sarcopenia in CLD alongside a discussion of existing and potential new treatment strategies.

Muscle NAD+ depletion and Serpina3n as molecular determinants of murine cancer cachexia—the effects of blocking myostatin and activins

ObjectiveCancer cachexia and muscle loss are associated with increased morbidity and mortality. In preclinical animal models, blocking activin receptor (ACVR) ligands has improved survival and prevented muscle wasting in cancer cachexia without an effect on tumour growth. However, the underlying mechanisms are poorly understood. This study aimed to identify cancer cachexia and soluble ACVR (sACVR) administration-evoked changes in muscle proteome. MethodsHealthy and C26 tumour-bearing (TB) mice were treated with recombinant sACVR. The sACVR or PBS control were administered either prior to the tumour formation or by continued administration before and after tumour formation. Muscles were analysed by quantitative proteomics with further examination of mitochondria and nicotinamide adenine dinucleotide (NAD+) metabolism. To complement the first prophylactic experiment, sACVR (or PBS) was injected as a treatment after tumour cell inoculation. ResultsMuscle proteomics in TB cachectic mice revealed downregulated signatures for mitochondrial oxidative phosphorylation (OXPHOS) and increased acute phase response (APR). These were accompanied by muscle NAD+ deficiency, alterations in NAD+ biosynthesis including downregulation of nicotinamide riboside kinase 2 (Nrk2), and decreased muscle protein synthesis. The disturbances in NAD+ metabolism and protein synthesis were rescued by treatment with sACVR. Across the whole proteome and APR, in particular, Serpina3n represented the most upregulated protein and the strongest predictor of cachexia. However, the increase in Serpina3n expression was associated with increased inflammation rather than decreased muscle mass and/or protein synthesis. ConclusionsWe present evidence implicating disturbed muscle mitochondrial OXPHOS proteome and NAD+ homeostasis in experimental cancer cachexia. Treatment of TB mice with a blocker of activin receptor ligands restores depleted muscle NAD+ and Nrk2, as well as decreased muscle protein synthesis. These results indicate putative new treatment therapies for cachexia and that although acute phase protein Serpina3n may serve as a predictor of cachexia, it more likely reflects a condition of elevated inflammation.

Cachexia Disrupts Diurnal Regulation of Activity, Feeding, and Muscle Mechanistic Target of Rapamycin Complex 1 in Mice.

Cancer cachexia is characterized by severe skeletal muscle mass loss, which is driven by decreased muscle protein synthesis and increased protein degradation. Daily physical activity and feeding behaviors exhibit diurnal fluctuations in mice that can impact the systemic environment and skeletal muscle signaling. We investigated the effect of cancer cachexia on the diurnal regulation of feeding, physical activity, and skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) signaling in tumor-bearing mice. We also examined the impact of increased physical activity on diurnal behaviors and skeletal muscle mTROC1 signaling in the cancer environment. Physical activity and feeding behaviors were measured for four consecutive days before sacrifice in male C57BL/6 (B6; n = 24) and Apc (MIN; n = 22) mice at 7:00 AM and 7:00 PM under ad libitum condition. A subset of B6 (n = 16) and MIN (n = 19) mice were given wheel access for 2 wk before diurnal behavior measurements. Gastrocnemius muscle protein expression was examined. The MIN mice demonstrated altered diurnal fluctuations in feeding and activity compared with the B6. Interestingly, cachexia did not alter MIN total food intake, but dramatically reduced cage physical activity. As a measurement of mTORC1 activity, 4E-BP1 phosphorylation increased after the dark cycle in B6 and precachectic MIN mice, whereas rpS6 phosphorylation was only increased after the dark cycle in MIN mice. MIN 4E-BP1 phosphorylation at the end of the light cycle was significantly correlated with cachexia progression and reduced physical activity. Voluntary wheel running increased light cycle MIN 4E-BP1 phosphorylation and attenuated muscle mass loss. The cancer environment can alter diurnal feeding and physical activity behaviors in tumor-bearing mice, which are linked to the progression of cachexia and muscle wasting. Furthermore, suppressed physical activity during cachexia is associated with decreased skeletal muscle mTORC1 signaling.

Protein malnutrition prevents heat conservation induced by amino acid infusion during general anesthesia in rats

The intravenous administration of an amino acid (AA) mixture during general anesthesia reduces anesthesia-induced hypothermia. AA-induced skeletal muscle protein synthesis and thermogenesis play important roles in the antihypothermic effects of AAs. We hypothesized that a preanesthetic dietary protein deficiency impairs the antihypothermic effects of AAs during general anesthesia due to a reduction in thermogenesis caused by a decrease in muscle protein synthesis. Sprague-Dawley rats were divided into 4 groups: fed a control diet plus saline (CON-SAL) or the AA mixture (CON-AA), and fed a protein-free diet plus saline (PF-SAL) or the AA mixture (PF-AA). SAL solution or AA mixture solution was infused for 180 minutes during sevoflurane anesthesia, and rectal temperatures were measured. Rectal temperatures were significantly higher in the CON-AA group than in the PF-AA group 90 to 180 minutes after initiating the intravenous infusion of the test solutions. There was no significant difference between the PF-SAL and PF-AA groups. Plasma insulin concentrations were significantly higher in the CON-AA group than in the PF-AA group (P < .05). The phosphorylation states of protein kinase B, mammalian target of rapamycin, and eukaryotic initiation factor 4E-binding protein 1 were significantly greater in the CON-AA group than in the PF-AA group (P < .05, P < .05, and P < .01, respectively). Our results indicated that a dietary protein deficiency before general anesthesia impaired the antihypothermic effects of an AA mixture infusion during general anesthesia by decreasing muscle protein synthesis through the insulin-stimulated phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin complex 1 signaling pathway followed by metabolic heat production.

Chronic heat stress affects muscle hypertrophy, muscle protein synthesis and uptake of amino acid in broilers via insulin like growth factor-mammalian target of rapamycin signal pathway

Heat stress markedly impairs the growth performance of broilers, such as the reduction of breast muscle mass and yield. The aim of this study was to examine the molecular mechanism of depressed muscle mass and yield caused by heat stress. A total of 144 (28-day-old) male broilers were allocated randomly into 3 treatment groups: (1) the normal control group (environment temperature was 22°C), (2) the heat stress group (environment temperature was 32°C), (3) the pair-fed group (environment temperature was 22°C and pair-fed to heat stress group). The experiment lasted for 14 d (from the age of 28 to 42 d). After 14 d of heat exposure, heat stress decreased (P < 0.05) broiler average daily gain, breast muscle mass, and muscle yield, and increased (P < 0.05) feed to gain ratio. After 14 d of heat exposure, heat stress increased (P < 0.05) the activities of aspartate aminotransferase and the concentrations of uric acid and most amino acids in serum, and reduced (P < 0.05) the concentration of insulin like growth factor 1 (IGF-1) in serum. Additionally, heat stress decreased (P < 0.05) the mRNA expressions of IGF-1, IGF-1 receptor, insulin receptor substrate 1, mammalian target of rapamycin (mTOR), the 70kD ribosomal protein S6 kinase, myogenic differentiation, myogenin, solute carrier family 38 member 2, solute carrier family 7 member 5, and solute carrier family 3 member 2 of the breast muscle. In conclusion, chronic heat stress resulted in lower breast muscle mass and yield, and decreased muscle protein synthesis and amino acid transportation by downregulating IGFs-mTOR signal pathway. These findings have important practical significance in discovering effective means to alleviate muscle loss caused by chronic heat stress.

Effects of Transcutaneous Application of Carbon Dioxide on diabetic muscle atrophy

IntroductionDiabetes results in muscle atrophy, also called diabetic myopathy. Both the increase in muscle proteolysis and the decrease in muscle protein synthesis contribute to diabetic muscle atrophy. Transcutaneous application of carbon dioxide (CO2) has been used for cardiac disease and skin problems for a long time. In addition, it has been reported the CO2 treatment leads to an increase of muscle mass in normal rats. Therefore, the transcutaneous application of CO2 would have a therapeutic potential for diabetic muscle atrophy. The aim of the present study was to investigate the effects of transcutaneous application of CO2 on diabetic muscle atrophy.MethodsMale Goto‐kakizaki rats were divided into control and CO2 treatment groups. The hair on the lower limbs was shaved and the hydrogel was applied. The CO2 adaptor was attached to the limbs and sealed, and CO2 was administered into the adaptor for 30 min. This treatment was performed everyday for 8 weeks.ResultsThe body weight, epididymal and retroperitoneal fat were lower in the CO2 treatment group than in the control. In addition, the level of fasting blood glucose in the CO2 treatment group was significantly decreased compared with the control. Furthermore, the muscle masses of lower limbs in the CO2 treatment group were higher than those in the control.ConclutionThese results indicate that the transcutaneous CO2 treatment may have a therapeutic potential for diabetic muscle atrophy.Support or Funding InformationSupported by Grants‐in‐Aid for Science Research from the Japanese MEXT.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Sarcopenia and Exercise “The State of the Art”

Skeletal muscle mass reduction might be a consequence of aging (sarcopenia), disease (cachexia) or inactivity (muscle atrophy). Studying the triggering factors leading to muscle loss is important in developing therapies to preserve muscle tissue function. The loss of skeletal muscle proteins is caused by an imbalance between the rate of their synthesis and degradation. Specifically, the conditions characterized by muscle loss involve an adaptation metabolism of increased protein degradation (cachexia), decreased muscle protein synthesis (inactivity), or alteration in both (sarcopenia). Sarcopenia and exercise is the main topic chosen for this review. This is a huge health problem, poorly discussed in the current literature and the aim of this review is to explain and help readers to better understand the differences between “sarcopenia”, “cachexia”, “muscle atrophy” and the relative beneficial effects of exercise used as a possible therapeutic intervention. Sarcopenia is a component of the fragility syndrome and indicates a significant health issue related to the progressive decline of muscle tissue quality and strength. Exercise is associated with improved life quality, reduced health problems, and prolonged lifespan. The latter suggests that exercise should be considered a fundamental point in the treatment of pathological skeletal muscle mass reduction. The present scientific contribution also seeks to emphasize to the scientific community the positive effects of the adapted physical activity in the elderly as a possible non-pharmacologic treatment to prevent or treat muscle atrophy.

Association between Sarcopenic Obesity and Metabolic Syndrome in Postmenopausal Women: A Cross-sectional Study Based on the Korean National Health and Nutritional Examination Surveys from 2008 to 2011.

BackgroundMenopause contributes to an increase in visceral fat mass and a decrease in muscle protein synthesis. Therefore, we performed this study to examine their relationship how effect the changes of body composition as obesity and sarcopenia on metabolic syndrome (MS) as a predictor of cardiovascular disease in postmenopausal women.MethodsUsing data from the Korean National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2011, we estimated that 4,183 postmenopausal women underwent dual energy X-ray absorptiometry scans. Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight that was less than 1 standard deviation below the sex specific mean for the young reference group. After classification into four groups, the results were adjusted with menopausal age and hormonal treatment. The relationship between sarcopenic obesity (SO) and MS in postmenopausal women was analyzed by logistic regression analysis in a complex sampling.ResultsIn an unadjusted model, the odds ratio (OR) of MS for sarcopenia was 1.94 (95% confidence interval [CI], 1.52-2.49); the obesity group had an OR of 4.55 (95% CI, 3.63-5.71); and distinctly, the SO group had an OR of 6.26 (95% CI, 5.10-7.70). Even though there was controlling for variable adjustment, no definite difference was seen in the results.ConclusionsSarcopenia and obesity were associated with MS independent of other metabolic impairment risk factors in both early menopausal and postmenopausal women. The results showed that, in particular, the prevalence of MS has increased more in postmenopausal women compared with previous research.

Marginal dietary zinc deprivation augments sepsis-induced alterations in skeletal muscle TNF-α but not protein synthesis.

Severe zinc deficiency is associated with an increased systemic inflammatory response and mortality after sepsis. However, the impact of mild zinc deficiency, which is more common in populations with chronic illnesses and sepsis, is unknown. In this study, we hypothesized that marginal dietary Zn deprivation (ZM) would amplify tissue inflammation and exacerbate the sepsis‐induced decrease in muscle protein synthesis. Adult male C57BL/6 mice were fed a zinc‐adequate (ZA) or ZM diet (30 or 10 mg Zn/kg, respectively) over 4 weeks, peritonitis was induced by cecal ligation and puncture (CLP), and mice were examined at either 24 h (acute) or 5 days (chronic) post‐CLP. Acute sepsis decreased the in vivo rate of skeletal muscle protein synthesis and the phosphorylation of the mTOR substrate 4E‐BP1. Acutely, sepsis increased TNF‐α and IL‐6 mRNA in muscle, and the increase in TNF‐α was significantly greater in ZM mice. However, muscle protein synthesis and 4E‐BP1 phosphorylation returned to baseline 5 days post‐CLP in both ZA and ZM mice. Protein degradation via markers of the ubiquitin proteasome pathway was increased in acute sepsis, yet only MuRF1 mRNA was increased in chronic sepsis and ZM amplified this elevation. Our data suggest that mild zinc deficiency increases TNF‐α in muscle acutely after sepsis but does not significantly modulate the rate of muscle protein synthesis.

Systemic blockade of ACVR2B ligands prevents chemotherapy-induced muscle wasting by restoring muscle protein synthesis without affecting oxidative capacity or atrogenes.

Doxorubicin is a widely used and effective chemotherapy drug. However, cardiac and skeletal muscle toxicity of doxorubicin limits its use. Inhibiting myostatin/activin signalling can prevent muscle atrophy, but its effects in chemotherapy-induced muscle wasting are unknown. In the present study we investigated the effects of doxorubicin administration alone or combined with activin receptor ligand pathway blockade by soluble activin receptor IIB (sACVR2B-Fc). Doxorubicin administration decreased body mass, muscle size and bone mineral density/content in mice. However, these effects were prevented by sACVR2B-Fc administration. Unlike in many other wasting situations, doxorubicin induced muscle atrophy without markedly increasing typical atrogenes or protein degradation pathways. Instead, doxorubicin decreased muscle protein synthesis which was completely restored by sACVR2B-Fc. Doxorubicin administration also resulted in impaired running performance without effects on skeletal muscle mitochondrial capacity/function or capillary density. Running performance and mitochondrial function were unaltered by sACVR2B-Fc administration. Tumour experiment using Lewis lung carcinoma cells demonstrated that sACVR2B-Fc decreased the cachectic effects of chemotherapy without affecting tumour growth. These results demonstrate that blocking ACVR2B signalling may be a promising strategy to counteract chemotherapy-induced muscle wasting without damage to skeletal muscle oxidative capacity or cancer treatment.

Acute Alcohol-Induced Decrease in Muscle Protein Synthesis in Female Mice Is REDD-1 and mTOR-Independent.

To determine the causative role of the REDD (regulated in development and DNA damage)-1 protein, a known negative regulator of mTOR kinase, in changes in muscle protein synthesis induced by acute alcohol administration. Adult female REDD1(-/-) or wild-type (WT) mice were injected IP with ethanol (alcohol; 3 g/kg BW) or saline and the skeletal muscle was removed 1 h later. In vivo protein synthesis was assessed as were selected endpoints related to the activation of mTOR and protein degradation. Acute alcohol decreased muscle protein synthesis similarly in WT and REDD1(-/-) mice. In contrast, mTORC1 signaling was largely unaffected by either EtOH or genotype as evidenced by the lack of change in the phosphorylation of its downstream targets, S6K1 T(389) and 4E-BP1 S(65). Although alcohol decreased p62 and ULK1 S(757) protein in muscle from WT and REDD1(-/-) mice, there was no change in LC3B lipidation, or beclin1, Atg7 and Atg12 protein suggesting no change in autophagy. MuRF1 and atrogin-1 mRNAs were elevated in alcohol-treated REDD1(-/-) mice compared with WT mice suggesting activation of the ubiquitin proteasome activity. While there was no genotype or alcohol effect on plasma corticosterone, REDD1(-/-) mice failed to demonstrate the alcohol-induced hyperinsulinemia seen in WT mice. REDD1 does not appear to play a role in the acute alcohol-mediated decrease in protein synthesis or mTOR activity, but may contribute to the regulation of ubiquitin-proteasome mediated protein breakdown.