In order to preserve muscle mass during catabolic states, investigators are actively searching for a specific inhibitor of MuRF1, the only known E3 ligase that can target muscle contractile proteins for their degradation. However, what would be the consequences of such inhibitors on other organs, both in the short and long term? Indeed, skeletal muscles can provide amino acids for liver gluconeogenesis, which is a crucial adaptation for maintaining glucose homeostasis upon elevated energy demands (e.g.
View Article and Find Full Text PDFT cell therapy strategies, from allogeneic stem cell transplantation toward genetically-modified T cells infusion, develop powerful anti-tumor effects but are often accompanied by side effects and their efficacy remains sometimes to be improved. It therefore appears important to provide a flexible and easily reversible gene expression regulation system to control T cells activity. We developed a gene expression regulation technology that exploits the physiological GCN2-ATF4 pathway's ability to induce gene expression in T cells in response to one essential amino acid deficiency.
View Article and Find Full Text PDFActivating transcription factor 4 (ATF4) is involved in muscle atrophy through the overexpression of some atrogenes. However, it also controls the transcription of genes involved in muscle homeostasis maintenance. Here, we explored the effect of ATF4 activation by the pharmacological molecule halofuginone during hindlimb suspension (HS)-induced muscle atrophy.
View Article and Find Full Text PDFChronic treatment with acetaminophen (APAP) induces cysteine (Cys) and glutathione (GSH) deficiency which leads to adverse metabolic effects including muscle atrophy. Mammalian cells respond to essential amino acid deprivation through the phosphorylation of the eukaryotic translation initiation factor 2α (eIF2α). Phosphorylated eIF2α leads to the recruitment of activating transcription factor 4 (ATF4) to specific CCAAT/enhancer-binding protein-ATF response element (CARE) located in the promoters of target genes.
View Article and Find Full Text PDFMiddle-aged and master endurance athletes exhibit similar physical performance and long-term muscle adaptation to aerobic exercise. Nevertheless, we hypothesized that the short-term plasticity of the skeletal muscle might be distinctly altered for master athletes when they are challenged by a single bout of prolonged moderate-intensity exercise. Six middle-aged (37Y) and five older (50Y) master highly-trained athletes performed a 24-h treadmill run (24TR).
View Article and Find Full Text PDFThis study evaluates the capacity of a bread enriched with fermentable dietary fibres to modulate the metabolism and nutrients handling between tissues, gut and peripheral, in a context of overfeeding. Net fluxes of glucose, lactate, urea, short chain fatty acids (SCFA), and amino acids were recorded in control and overfed female mini-pigs supplemented or not with fibre-enriched bread. SCFA in fecal water and gene expressions, but not protein levels or metabolic fluxes, were measured in muscle, adipose tissue, and intestine.
View Article and Find Full Text PDFChronic Mg deficiency is the underlying cause of a broad range of health dysfunctions. As 25% of body Mg is located in the skeletal muscle, Mg transport and homeostasis systems (MgTHs) in the muscle are critical for whole-body Mg homeostasis. In the present study, we assessed whether Mg deficiency alters muscle fiber characteristics and major pathways regulating muscle physiology.
View Article and Find Full Text PDF(1) Background: Aging is associated with a progressive decline in muscle mass and function. Aging is also a primary risk factor for metabolic syndrome, which further alters muscle metabolism. However, the molecular mechanisms involved remain to be clarified.
View Article and Find Full Text PDFMitochondria alterations are a classical feature of muscle immobilization, and autophagy is required for the elimination of deficient mitochondria (mitophagy) and the maintenance of muscle mass. We focused on the regulation of mitochondrial quality control during immobilization and remobilization in rat gastrocnemius (GA) and tibialis anterior (TA) muscles, which have very different atrophy and recovery kinetics. We studied mitochondrial biogenesis, dynamic, movement along microtubules, and addressing to autophagy.
View Article and Find Full Text PDFMagnesium (Mg) is critical for a number of biological processes and 25% body Mg is located in the skeletal muscle. Mg transport and homeostasis systems (MgTHs) regulate intracellular Mg concentration and muscle MgTHs are thus related to whole body Mg homeostasis. Nonetheless, few studies have investigated the regulation of muscle MgTHs under (patho)physiological conditions.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Biol Lipids
February 2020
Rheumatoid arthritis (RA) has a negative impact on muscle mass, and reduces patient's mobility and autonomy. Furthermore, RA is associated with metabolic comorbidities, notably in lipid homeostasis by unknown mechanisms. To understand the links between the loss in muscle mass and the metabolic abnormalities, arthritis was induced in male Sprague Dawley rats (n = 11) using the collagen-induced arthritis model.
View Article and Find Full Text PDFSickle cell disease (SCD) is a genetic hemoglobinopathy leading to 2 major clinical manifestations: severe chronic hemolytic anemia and iterative vaso-occlusive crises. SCD is also accompanied by profound muscle microvascular remodeling. The beneficial effects of endurance training on microvasculature are widely known.
View Article and Find Full Text PDFObesity induced by overfeeding ultimately can lead to nonalcoholic fatty liver disease, whereas dietary fiber consumption is known to have a beneficial effect. We aimed to determine if a supplementation of a mix of fibers (inulin, resistant starch and pectin) could limit or alleviate overfeeding-induced metabolic perturbations. Twenty female minipigs were fed with a control diet (C) or an enriched fat/sucrose diet supplemented (O + F) or not (O) with fibers.
View Article and Find Full Text PDFSkeletal muscle mass is reduced during many diseases or physiological situations (disuse, aging), which results in decreased strength and increased mortality. Muscle mass is mainly controlled by the ubiquitin-proteasome system (UPS), involving hundreds of ubiquitinating enzymes (E2s and E3s) that target their dedicated substrates for subsequent degradation. We recently demonstrated that MuRF1, an E3 ubiquitin ligase known to bind to sarcomeric proteins (telethonin, α-actin, myosins) during catabolic situations, interacts with 5 different E2 enzymes and that these E2-MuRF1 couples are able to target telethonin, a small sarcomeric protein, for degradation.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
October 2018
Background: Glucocorticoids (GC) play a major role in muscle atrophy. As skeletal muscle is a secretory organ, characterization of the muscle secretome elicited by muscle atrophy should allow to better understand the cellular mechanisms and to identify circulating biomarkers of this condition. Our project aimed to identify the changes in the muscle secretome associated with GC-induced muscle atrophy and susceptible to translate into circulation.
View Article and Find Full Text PDFMass spectrometry imaging (MSI) is a powerful tool to visualize the spatial distribution of molecules on a tissue section. The main limitation of MALDI-MSI of proteins is the lack of direct identification. Therefore, this study focuses on a MSI~LC-MS/MS-LF workflow to link the results from MALDI-MSI with potential peak identification and label-free quantitation, using only one tissue section.
View Article and Find Full Text PDFAging strongly affects the skeletal muscle and is associated with microvascular dysfunctions. Age is also a primary risk factor for the metabolic syndrome, which is a cluster of metabolic and cardiovascular symptoms. Among the metabolic syndrome components, hypertension is the most prevalent in elderly subjects and has a central role in vascular alterations.
View Article and Find Full Text PDFBackground: Muscle ageing contributes to both loss of functional autonomy and increased morbidity. Muscle atrophy accelerates after 50 years of age, but the mechanisms involved are complex and likely result from the alteration of a variety of interrelated functions. In order to better understand the molecular mechanisms underlying muscle chronological ageing in human, we have undertaken a top-down differential proteomic approach to identify novel biomarkers after the fifth decade of age.
View Article and Find Full Text PDFOne of the most noticeable effects of aging is the reduction in skeletal muscle mass and strength (sarcopenia). The metabolic syndrome (MS) is also prevalent in old subjects, but its relevance to skeletal muscle characteristics has poorly been investigated. Immunohistochemical studies were performed with muscle biopsies from young (22 years) and old (73 years) men with and without MS to reveal age-dependent and MS-associated modifications of fiber-type characteristics.
View Article and Find Full Text PDFThe age-related loss of skeletal muscle mass and function (sarcopenia) is a consistent hallmark of ageing. Apoptosis plays an important role in muscle atrophy, and the intent of this study was to specify whether apoptosis is restricted to myofibre nuclei (myonuclei) or occurs in satellite cells or stromal cells of extracellular matrix (ECM). Sarcopenia in mouse gastrocnemius muscle was characterized by myofibre atrophy, oxidative type grouping, delocalization of myonuclei and ECM fibrosis.
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