DNA Methylation in the Adaptive Response to Exercise.

Emerging evidence published over the past decade has highlighted the role of DNA methylation in skeletal muscle function and health, including as an epigenetic transducer of the adaptive response to exercise. In this review, we aim to synthesize the latest findings in this field to highlight: (1) the shifting understanding of the genomic localization of altered DNA methylation in response to acute and chronic aerobic and resistance exercise in skeletal muscle (e.g.

Voluntary wheel running improves molecular and functional deficits in a murine model of facioscapulohumeral muscular dystrophy.

Endurance exercise training is beneficial for skeletal muscle health, but it is unclear if this type of exercise can target or correct the molecular mechanisms of facioscapulohumeral muscular dystrophy (FSHD). Using the FLExDUX4 murine model of FSHD characterized by chronic, low levels of pathological double homeobox protein 4 () gene expression, we show that 6 weeks of voluntary, free wheel running improves running performance, strength, mitochondrial function, and sarcolemmal repair capacity, while slowing/reversing skeletal muscle fibrosis. These improvements are associated with restored transcriptional activity of gene networks/pathways regulating actin cytoskeletal signaling, vascular remodeling, inflammation, fibrosis, and muscle mass toward wild-type (WT) levels.

Molecular and Phenotypic Changes in FLExDUX4 Mice.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the aberrant expression of the double homeobox 4 () gene. The mouse model carries an inverted human transgene which has leaky transgene expression at a very low level. No overt muscle pathology was reported before 16 weeks.

Facioscapulohumeral Muscular Dystrophy is Associated With Altered Myoblast Proteome Dynamics.

Proteomic studies in facioscapulohumeral muscular dystrophy (FSHD) could offer new insight into disease mechanisms underpinned by post-transcriptional processes. We used stable isotope (deuterium oxide; DO) labeling and peptide mass spectrometry to investigate the abundance and turnover rates of proteins in cultured muscle cells from two individuals affected by FSHD and their unaffected siblings (UASb). We measured the abundance of 4420 proteins and the turnover rate of 2324 proteins in each (n = 4) myoblast sample.

Worksite-based intensive lifestyle therapy has profound cardiometabolic benefits in people with obesity and type 2 diabetes.

Lifestyle therapy (energy restriction and exercise) is the cornerstone of therapy for people with type 2 diabetes (T2D) but is difficult to implement. We conducted an 8-month randomized controlled trial in persons with obesity and T2D (17 women and 1 man) to determine the therapeutic effects and potential mechanisms of intensive lifestyle therapy on cardiometabolic function. Intensive lifestyle therapy was conducted at the worksite to enhance compliance and resulted in marked (17%) weight loss and beneficial changes in body fat mass, intrahepatic triglyceride content, cardiorespiratory fitness, muscle strength, glycemic control, β cell function, and multi-organ insulin sensitivity, which were associated with changes in muscle NAD biosynthesis, sirtuin signaling, and mitochondrial function and in adipose tissue remodeling.

Resistance exercise training with protein supplementation improves skeletal muscle strength and improves quality of life in late adolescents and young adults with Barth syndrome: A pilot study.

Background: Muscle weakness and exercise intolerance contribute to reduced quality of life (QOL) in Barth syndrome (BTHS). Our group previously found that 12 weeks of resistance exercise training (RET) improved muscle strength, however, did not increase muscle (lean) mass or QOL in n = 3 young adults with BTHS. The overall objective of this pilot study was to examine the safety and effectiveness of RET plus daily protein supplementation (RET + protein) on muscle strength, skeletal muscle mass, exercise tolerance, cardiac function, and QOL in late adolescents/young adults with BTHS.

Deficits in the Skeletal Muscle Transcriptome and Mitochondrial Coupling in Progressive Diabetes-Induced CKD Relate to Functional Decline.

Two-thirds of people with type 2 diabetes mellitus (T2DM) have or will develop chronic kidney disease (CKD), which is characterized by rapid renal decline that, together with superimposed T2DM-related metabolic sequelae, synergistically promotes early frailty and mobility deficits that increase the risk of mortality. Distinguishing the mechanisms linking renal decline to mobility deficits in CKD progression and/or increasing severity in T2DM is instrumental both in identifying those at high risk for functional decline and in formulating effective treatment strategies to prevent renal failure. While evidence suggests that skeletal muscle energetics may relate to the development of these comorbidities in advanced CKD, this has never been assessed across the spectrum of CKD progression, especially in T2DM-induced CKD.

Arginine kinetics are altered in a pilot sample of adolescents and young adults with Barth syndrome.

Barth syndrome (BTHS) is a rare, X-linked cardiomyopathy that is characterized by abnormalities in glucose and lipid metabolism, with less known regarding amino acid metabolism. This pilot study characterized whole-body arginine kinetics and found lower arginine rate of appearance into plasma (0.69 ± 0.

DUX4 Transcript Knockdown with Antisense 2'-O-Methoxyethyl Gapmers for the Treatment of Facioscapulohumeral Muscular Dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by a progressive, asymmetric weakening of muscles, starting with those in the upper body. It is caused by aberrant expression of the double homeobox protein 4 gene (DUX4) in skeletal muscle. FSHD is currently incurable.

A Single Bout of Premeal Resistance Exercise Improves Postprandial Glucose Metabolism in Obese Men with Prediabetes.

Introduction: Prediabetes is a major risk factor for type 2 diabetes and cardiovascular diseases. Although resistance exercise (RE) is recommended for individuals with prediabetes, the effects of RE on postprandial glucose metabolism in this population are poorly understood. Therefore, the purpose of this study was to elucidate how RE affects postprandial glucose kinetics, insulin sensitivity, beta cell function, and glucose oxidation during the subsequent meal in sedentary men with obesity and prediabetes.

Membrane Repair Deficit in Facioscapulohumeral Muscular Dystrophy.

Deficits in plasma membrane repair have been identified in dysferlinopathy and Duchenne Muscular Dystrophy, and contribute to progressive myopathy. Although Facioscapulohumeral Muscular Dystrophy (FSHD) shares clinicopathological features with these muscular dystrophies, it is unknown if FSHD is characterized by plasma membrane repair deficits. Therefore, we exposed immortalized human FSHD myoblasts, immortalized myoblasts from unaffected siblings, and myofibers from a murine model of FSHD () to focal, pulsed laser ablation of the sarcolemma.

A single bout of resistance exercise improves postprandial lipid metabolism in overweight/obese men with prediabetes.

Aims/hypothesis: Prediabetes is associated with postprandial hypertriacylglycerolaemia. Resistance exercise acutely lowers postprandial plasma triacylglycerol (TG); however, the changes in lipid metabolism that mediate this reduction are poorly understood. The aim of this study was to identify the constitutive metabolic mechanisms underlying the changes in postprandial lipid metabolism after resistance exercise in obese men with prediabetes.

Myocardial glucose and fatty acid metabolism is altered and associated with lower cardiac function in young adults with Barth syndrome.

Background: Barth syndrome (BTHS) is a rare X-linked condition resulting in cardiomyopathy, however; the effects of BTHS on myocardial substrate metabolism and its relationships with cardiac high-energy phosphate metabolism and left ventricular (LV) function are unknown. We sought to characterize myocardial glucose, fatty acid (FA), and leucine metabolism in BTHS and unaffected controls and examine their relationships with cardiac high-energy phosphate metabolism and LV function.

Methods/results: Young adults with BTHS (n = 14) and unaffected controls (n = 11, Control, total n = 25) underwent bolus injections of O-water and 1-C-glucose, palmitate, and leucine and concurrent positron emission tomography imaging.

Blunted fat oxidation upon submaximal exercise is partially compensated by enhanced glucose metabolism in children, adolescents, and young adults with Barth syndrome.

Barth syndrome (BTHS) is a rare X-linked condition resulting in abnormal mitochondria, cardioskeletal myopathy, and growth delay; however, the effects of BTHS on substrate metabolism regulation and their relationships with tissue function in humans are unknown. We sought to characterize glucose and fat metabolism during rest, submaximal exercise, and postexercise rest in children, adolescents, and young adults with BTHS and unaffected controls and examine their relationships with cardioskeletal energetics and function. Children/adolescents and young adults with BTHS (n = 29) and children/adolescent and young adult control participants (n = 28, total n = 57) underwent an infusion of 6'6'H2 glucose and U- C palmitate and indirect calorimetry during rest, 30-minutes of moderate exercise (50% ), and recovery.

Peak oxygen uptake (VO2peak) across childhood, adolescence and young adulthood in Barth syndrome: Data from cross-sectional and longitudinal studies.

Unlabelled: Barth syndrome (BTHS) is an ultra-rare, X-linked recessive disorder characterized by cardio-skeletal myopathy, exercise intolerance, and growth delay. Oxygen uptake during peak exercise (VO2peak) has been shown to be severely limited in individuals with BTHS however; the trajectory of VO2peak from childhood to young adulthood is unknown. The objective of this study was to describe VO2peak from childhood through young adulthood in BTHS.

Reduced Muscle Strength in Barth Syndrome May Be Improved by Resistance Exercise Training: A Pilot Study.

Background: Cardioskeletal myopathy is thought to contribute to exercise intolerance, and reduced quality of life (QOL) in Barth syndrome (BTHS). The objectives of this study were to examine: (1) skeletal muscle strength/performance in adolescents and young adults with BTHS and (2) the safety, feasibility, and initial efficacy of 12 weeks of progressive resistance exercise training (RET) on muscle strength, mass, and performance, bone mineral density, exercise tolerance, cardiac function, and QOL in individuals with BTHS.

Methods: Individuals with BTHS (n = 9, 23 ± 6 years), and age-, sex-, and activity level-matched unaffected Controls (n = 7, 26 ± 5 years) underwent baseline testing to assess muscle performance, exercise capacity, cardiac structure and function, body composition, and health-related QOL.

Early-Onset Physical Frailty in Adults With Diabesity and Peripheral Neuropathy.

Objectives: Diabesity (obesity and diabetes mellitus) has been identified as a potential contributor to early-onset frailty. Impairments contributing to early onset of physical frailty in this population are not well understood, and there is little evidence of the impact of peripheral neuropathy on frailty. The purpose of this study was to determine impairments that contribute to early-onset physical frailty in individuals with diabesity and peripheral neuropathy.

Impaired cardiac and skeletal muscle bioenergetics in children, adolescents, and young adults with Barth syndrome.

Unlabelled: Barth syndrome (BTHS) is an X-linked condition characterized by altered cardiolipin metabolism and cardioskeletal myopathy. We sought to compare cardiac and skeletal muscle bioenergetics in children, adolescents, and young adults with BTHS and unaffected controls and examine their relationships with cardiac function and exercise capacity. Children/adolescents and young adults with BTHS ( = 20) and children/adolescent and young adult control participants ( = 23, total  = 43) underwent P magnetic resonance spectroscopy (P-MRS) of the lower extremity (calf) and heart for estimation of skeletal muscle and cardiac bioenergetics.

Improving Exercise Performance with an Accelerometer-Based Smartphone App: A Randomized Controlled Trial.

Objective: Proper exercise form is critical for the safety and efficacy of therapeutic exercise. This research examines if a novel smartphone application, designed to monitor and provide real-time corrections during resistance training, can reduce performance errors and elicit a motor learning response.

Design: Forty-two participants aged 18 to 65 years were randomly assigned to treatment and control groups.

Explanators of Sarcopenia in Individuals With Diabesity: A Cross-Sectional Analysis.

Background And Purpose: Excess lower extremity intermuscular adipose tissue (IMAT), reduced strength, and functional limitations are common in obese individuals with and without diabetes (the former termed diabesity). Individuals with diabesity are particularly susceptible to accelerated sarcopenia, which may be underdiagnosed. The purpose of this study was to determine critical values for leg IMAT volume, plantar flexor (PF) muscle strength, and physical performance that help identify individuals with diabesity who have sarcopenia.

Accuracy and Precision of an Accelerometer-Based Smartphone App Designed to Monitor and Record Angular Movement over Time.

Background: Therapeutic exercise is a central component in the management of many common conditions. It is imperative, therefore, that clinicians monitor and correct patient performance to facilitate the use of proper form both in the clinic and during home exercise programs. Although clinicians are trained to prescribe exercise and analyze form, there are many subtleties that may be missed by relying on visual assessment.

Adipose tissue content, muscle performance and physical function in obese adults with type 2 diabetes mellitus and peripheral neuropathy.

Aims: To determine leg intermuscular (IMAT) and subcutaneous (SQAT) adipose tissue and their relationships with muscle performance and function in obese adults with and without type 2 diabetes and peripheral neuropathy (T2DMPN).

Methods: Seventy-nine age-matched obese adults were studied, 13 T2DM, 54 T2DMPN, and 24 obese controls. Leg fat (%IMAT, %SQAT) volumes were quantified using MRI.