The autophagy inhibitor NSC185058 suppresses mTORC1-mediated protein anabolism in cultured skeletal muscle.

The mammalian target of rapamycin (mTOR), and specifically the mTOR complex 1 (mTORC1) is the central regulator of anabolism in skeletal muscle. Among the many functions of this kinase complex is the inhibition of the catabolic process of autophagy; however, less work has been done in investigating the role of autophagy in regulating mTORC1 signaling. Using an in vitro model to better understand the pathways involved, we activated mTORC1 by several different means (growth factors, leucine supplementation, or muscle contraction), alone or with the autophagy inhibitor NSC185058.

The Effect of Choline and Resistance Training on Strength and Lean Mass in Older Adults.

Choline plays many important roles, including the synthesis of acetylcholine, and may affect muscle responses to exercise. We previously observed correlations between low choline intake and reduced gains in strength and lean mass following a 12-week resistance exercise training (RET) program for older adults. To further explore these findings, we conducted a randomized controlled trial.

Influence of Mechanistic Target of Rapamycin (mTOR)-Regulated Anabolic Pathways on Equine Skeletal Muscle Health.

Skeletal muscle is a highly dynamic organ that is essential for locomotion as well as endocrine regulation in all populations of horses. However, despite the importance of adequate muscle development and maintenance, the mechanisms underlying protein anabolism in horses on different diets, exercise programs, and at different life stages remain obscure. Mechanistic target of rapamycin (mTOR) is a key component of the protein synthesis pathway and is regulated by biological factors such as insulin and amino acid availability.

Myokines derived from contracting skeletal muscle suppress anabolism in MCF7 breast cancer cells by inhibiting mTOR.

There is strong evidence that physical activity has a profound protective effect against multiple types of cancer. Here, we show that this effect may be mediated by factors released from skeletal muscle during simulated exercise, , which suppress canonical anabolic signaling in breast cancer. We report attenuated growth of MCF7 breast cancer cells in the presence of a rodent-derived exercise conditioned perfusate, independent of prior exercise training.

Ablation of Ghrelin Receptor Mitigates the Metabolic Decline of Aging Skeletal Muscle.

The orexigenic hormone ghrelin has multifaceted roles in health and disease. We have reported that ablation of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), protects against metabolic dysfunction of adipose tissues in aging. Our further observation interestingly revealed that GHS-R deficiency phenocopies the effects of myokine irisin.

Muscle miR-16 deletion results in impaired insulin sensitivity and contractile function in a sex-dependent manner.

microRNAs (miRs) are linked to various human diseases including type 2 diabetes mellitus (T2DM) and emerging evidence suggests that miRs may serve as potential therapeutic targets. Lower miR-16 content is consistent across different models of T2DM; however, the role of miR-16 in muscle metabolic health is still elusive. Therefore, the purpose of this study was to investigate how deletion of miR-16 in mice affects skeletal muscle metabolic health and contractile function in both sexes.

Culprits or consequences: Understanding the metabolic dysregulation of muscle in diabetes.

The prevalence of type 2 diabetes (T2D) continues to rise despite the amount of research dedicated to finding the culprits of this debilitating disease. Skeletal muscle is arguably the most important contributor to glucose disposal making it a clear target in insulin resistance and T2D research. Within skeletal muscle there is a clear link to metabolic dysregulation during the progression of T2D but the determination of culprits consequences of the disease has been elusive.

Interorgan Metabolism of Amino Acids in Human Health and Disease.

Amino acids are integral for human health, influencing an array of physiological processes from gene expression to vasodilation to the immune response. In accordance with this expansive range of unique functions, the tissues of the body engage in a complex interplay of amino acid exchange and metabolism to respond to the organism's dynamic needs for a range of nitrogenous products. Interorgan amino acid metabolism is required for numerous metabolic pathways, including the synthesis of functional amino acids like arginine, glutamate, glutamine, and glycine.

Rider Energy Expenditure During High Intensity Horse Activity.

Despite the fact that horseback riding is a popular sport, there is little information available on horseback riding as a physical activity. The objective of this experiment was to quantify energy expenditure of participants (n=20) during three riding tests: a 45min walk-trot-canter ride (WTC), a reining pattern ride and a cutting simulation ride while wearing a telemetric gas analyzer. Total energy expenditure (tEE), mean and peak metabolic equivalents of task (MET), heart rate (HR), respiratory frequency (RF), relative oxygen consumption (relVO), and respiratory exchange ratio (RER) were assessed.

Regulation of cellular anabolism by mTOR: or how I learned to stop worrying and love translation.

The process and regulation of cellular metabolism are extremely complex and accomplished through multiple signalling pathways that operate in parallel, and often experience significant overlap in upstream and downstream a signal transduction. Despite this complexity, single pathway or even single protein activations are commonly used to extrapolate broad characterizations of cellular metabolism. Furthermore, multiple routes for peptide-chain translation initiation exist, some of which may be either exclusive or overlapping depending on the state and environment of the cell.

Regulation of mitochondrial quality following repeated bouts of hindlimb unloading.

Muscle disuse impairs muscle quality and is associated with increased mortality. Little is known regarding additive effects of multiple bouts of disuse, which is a common occurrence in patients experiencing multiple surgeries. Mitochondrial quality is vital to muscle health and quality; however, to date mitochondrial quality control has not been investigated following multiple bouts of disuse.

Effect of combined fish oil & Curcumin on murine skeletal muscle morphology and stress response proteins during mechanical unloading.

Skeletal muscle is a highly adaptable tissue capable of remodeling when dynamic stress is altered, including changes in mechanical loading and stretch. When muscle is subjected to an unloaded state (e.g.

The effects of hindlimb unloading versus dietary cholesterol and resistance training on rat skeletal muscle responses.

Background: The loss of muscle mass and concomitantly strength, poses a serious risk to the elderly and to astronauts. Dietary cholesterol (CL), in conjunction with resistance training (RT), has been strongly associated with improvements in lean mass. The purpose of this study was to examine the effects of two opposing environments on rat skeletal muscle: (1) hindlimb unloading and (2) CL and RT.

Responses of skeletal muscle size and anabolism are reproducible with multiple periods of unloading/reloading.

Mechanical unloading has long been understood to contribute to rapid and substantial adaptations within skeletal muscle, most notably, muscle atrophy. Studies have often demonstrated that many of the alterations resulting from disuse are reversed with a reintroduction of load and have supported the concept of muscle plasticity. We hypothesized that adaptations during disuse and recovery were a repeatable/reproducible phenomenon, which we tested with repeated changes in mechanical load.

Effect of Eukarion-134 on Akt-mTOR signalling in the rat soleus during 7 days of mechanical unloading.

New Findings: What is the central question of this study? Translocation of nNOSμ initiates catabolic signalling via FoxO3a and skeletal muscle atrophy during mechanical unloading. Recent evidence suggests that unloading-induced muscle atrophy and FoxO3a activation are redox sensitive. Will a mimetic of superoxide dismutase and catalase (i.

The influence of chronic IL-6 exposure, in vivo, on rat Achilles tendon extracellular matrix.

When compared to placebo, acetaminophen (APAP) reduces tendon stiffness and collagen cross-linking. APAP also enhances the exercise-induced increase in peritendinous levels of IL-6. Elevated levels of IL-6 are associated with tendinopathy, thus we hypothesized that chronic, elevated peritendinous IL-6 would alter tendon extracellular matrix (ECM).

Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle.

Insulin resistance is a well-known risk factor for obesity, metabolic syndrome (MetSyn) and associated cardiovascular diseases, but its mechanisms are undefined in the lymphatics. Mesenteric lymphatic vessels from MetSyn or LPS-injected rats exhibited impaired intrinsic contractile activity and associated inflammatory changes. Hence, we hypothesized that insulin resistance in lymphatic muscle cells (LMCs) affects cell bioenergetics and signaling pathways that consequently alter contractility.

Cumulative Muscle Protein Synthesis and Protein Intake Requirements.

Muscle protein synthesis (MPS) fluctuates widely over the course of a day and is influenced by many factors. The time course of MPS responses to exercise and the influence of training and nutrition can only be pieced together from several different investigations and methods, many of which create unnatural experimental conditions. Measurements of cumulative MPS, the sum synthesis over an extended period, using deuterium oxide have been shown to accurately reflect muscle responses and may allow investigations of the response to exercise, total protein intake requirements, and interaction with protein timing in free-living experimental conditions; these factors have yet to be carefully integrated.

Acute and chronic safety and efficacy of dose dependent creatine nitrate supplementation and exercise performance.

Background: Creatine monohydrate (CrM) and nitrate are popular supplements for improving exercise performance; yet have not been investigated in combination. We performed two studies to determine the safety and exercise performance-characteristics of creatine nitrate (CrN) supplementation.

Methods: Study 1 participants (N = 13) ingested 1.

microRNA-16 Is Downregulated During Insulin Resistance and Controls Skeletal Muscle Protein Accretion.

Insulin resistant diabetes, currently at epidemic levels in developed countries, begins in the skeletal muscle and is linked to altered protein turnover. microRNAs downregulate targeted mRNA translation decreasing the amount of translated protein, thereby regulating many cellular processes. Regulation of miRNAs and their function in skeletal muscle insulin resistance is largely unexplored.

Partial Support Ventilation and Mitochondrial-Targeted Antioxidants Protect against Ventilator-Induced Decreases in Diaphragm Muscle Protein Synthesis.

Mechanical ventilation (MV) is a life-saving intervention in patients in respiratory failure. Unfortunately, prolonged MV results in the rapid development of diaphragm atrophy and weakness. MV-induced diaphragmatic weakness is significant because inspiratory muscle dysfunction is a risk factor for problematic weaning from MV.

Effects of 28 days of beta-alanine and creatine supplementation on muscle carnosine, body composition and exercise performance in recreationally active females.

Background: The purpose of this study was to examine the short-term and chronic effects of β-ALA supplementation with and without creatine monohydrate on body composition, aerobic and anaerobic exercise performance, and muscle carnosine and creatine levels in college-aged recreationally active females.

Methods: Thirty-two females were randomized in a double-blind, placebo-controlled manner into one of four supplementation groups: β-ALA only (BA, n = 8), creatine only (CRE, n = 8), β-ALA and creatine combined (BAC, n = 9) and placebo (PLA, n = 7). Participants supplemented for four weeks included a loading phase for the creatine for week 1 of 0.