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Lucien Nadeau

Bio: Lucien Nadeau is an academic researcher from University of Ottawa. The author has contributed to research in topics: Skeletal muscle & Myokine. The author has an hindex of 4, co-authored 5 publications receiving 63 citations.

Papers
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Journal ArticleDOI
TL;DR: The literature is reviewed to propose a model for the regulation of IL-15 by the soluble form ofIL-15Rα, which results in a phenotype similar to that of overexpressing/oversecreting IL- 15 in mice to explain why some findings in the literature seem to be contradictory.
Abstract: Interleukin (IL)-15 is a cytokine with important immunological functions It is highly expressed in skeletal muscle and is believed to be a myokine, a hypothesis supported by the rapid increase in circulating levels of IL-15 in response to exercise Treatment with high doses of IL-15 results in metabolic adaptations such as improved insulin sensitivity and whole-body fatty acid oxidation and protection from high-fat-diet-induced obesity and insulin resistance IL-15 secreted by contracting muscle may therefore act as an endocrine factor to improve adiposity and energy metabolism in different tissues Most studies have used supraphysiological doses of IL-15 that do not represent circulating IL-15 in response to exercise However, evidence shows that IL-15 levels are higher in muscle interstitium and that IL-15 might improve muscle glucose homeostasis and oxidative metabolism in an autocrine/paracrine manner Nevertheless, how IL-15 signals in skeletal muscle to improve muscle energy metabolism is not understood completely, especially because the absence of the α subunit of the IL-15 receptor (IL-15Rα) results in a phenotype similar to that of overexpressing/oversecreting IL-15 in mice In this article, we review the literature to propose a model for the regulation of IL-15 by the soluble form of IL-15Rα to explain why some findings in the literature seem, at first glance, to be contradictory

47 citations

Journal ArticleDOI
TL;DR: It is shown for the first time that exposure to a dioxin-like PCB adversely affects skeletal muscle glucose metabolism and PCB126 could play an important role in the development of metabolic disorders.
Abstract: Polychlorinated biphenyls (PCBs) are increasingly recognized as metabolic disruptors. Due to its mass, skeletal muscle is the major site of glucose disposal. While muscle mitochondrial dysfunction and oxidative stress have been shown to play a central role in metabolic disease development, no studies to date have investigated the effect of PCB exposure on muscle energy metabolism and oxidative stress. In this pilot study, we tested the effect of exposure to PCB126 in L6 myotubes (from 1 to 2500 nM for 24 h) on mitochondrial function, glucose metabolism, and oxidative stress. Exposure to PCB126 had no apparent effect on resting, maximal, and proton leak-dependent oxygen consumption rate in intact L6 myotubes. However, basal glucose uptake and glycolysis were inhibited by 20-30 % in L6 myotubes exposed to PCB126. Exposure to PCB126 did not appear to alter skeletal muscle anti-oxidant defense or oxidative stress. In conclusion, our study shows for the first time that exposure to a dioxin-like PCB adversely affects skeletal muscle glucose metabolism. Given the importance of skeletal muscle in the maintenance of glucose homeostasis, PCB126 could play an important role in the development of metabolic disorders.

14 citations

Journal ArticleDOI
TL;DR: Ion-pair chromatography coupled to inductively coupled plasma mass spectrometry (ICP-MS) was evaluated and validated for the determination of arsenic species in fruit juice and fruit drink products as discussed by the authors.
Abstract: Ion-pair chromatography coupled to inductively coupled plasma mass spectrometry (ICP-MS) was evaluated and validated for the determination of arsenic species in fruit juice and fruit drink products. A Phenomenex analytical column (Prodigy 3 μ ODS (3) 4 μm × 2.0 mm × 150 mm) and a mobile phase consisting of 5 mmol l−1 malonic acid, 3 mmol l−1 of tetrabutylammonium hydroxide solution and 5 % methanol were used to achieve arsenic speciation separation. The arsenic species were detected at m/z 75 with an Agilent 7500cx ICP-MS. After demonstrating the method was sensitive, accurate and fit for purpose, and it was applied to analyze 96 fruit juice and fruit drink samples. Speciation analysis of the 96 fruit juice and fruit drink products revealed that inorganic arsenic was the major species found in the majority of juice products tested in the study. The concentration of inorganic arsenic (sum of As3+ and As5+) ranged from

10 citations


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Journal ArticleDOI
TL;DR: The main mechanisms used by metabolism-disrupting chemicals to alter energy balance are reviewed, which should help to identify new MDCs, as well as novel targets of their action.
Abstract: Energy balance involves the adjustment of food intake, energy expenditure and body fat reserves through homeostatic pathways These pathways include a multitude of biochemical reactions, as well as hormonal cues Dysfunction of this homeostatic control system results in common metabolism-related pathologies, which include obesity and type 2 diabetes mellitus Metabolism-disrupting chemicals (MDCs) are a particular class of endocrine-disrupting chemicals that affect energy homeostasis MDCs affect multiple endocrine mechanisms and thus different cell types that are implicated in metabolic control MDCs affect gene expression and the biosynthesis of key enzymes, hormones and adipokines that are essential for controlling energy homeostasis This multifaceted spectrum of actions precludes compensatory responses and favours metabolic disorders Herein, we review the main mechanisms used by MDCs to alter energy balance This work should help to identify new MDCs, as well as novel targets of their action

147 citations

OtherDOI
TL;DR: The possibilities and pitfalls of the quest for exercise mimetics, which are intended to target the molecular mechanisms underlying the beneficial effects of exercise on metabolic disease, are outlined.
Abstract: The skeletal muscle is the largest organ in the body, by mass. It is also the regulator of glucose homeostasis, responsible for 80% of postprandial glucose uptake from the circulation. Skeletal muscle is essential for metabolism, both for its role in glucose uptake and its importance in exercise and metabolic disease. In this article, we give an overview of the importance of skeletal muscle in metabolism, describing its role in glucose uptake and the diseases that are associated with skeletal muscle metabolic dysregulation. We focus on the role of skeletal muscle in peripheral insulin resistance and the potential for skeletal muscle-targeted therapeutics to combat insulin resistance and diabetes, as well as other metabolic diseases like aging and obesity. In particular, we outline the possibilities and pitfalls of the quest for exercise mimetics, which are intended to target the molecular mechanisms underlying the beneficial effects of exercise on metabolic disease. We also provide a description of the molecular mechanisms that regulate skeletal muscle glucose uptake, including a focus on the SNARE proteins, which are essential regulators of glucose transport into the skeletal muscle. © 2020 American Physiological Society. Compr Physiol 10:785-809, 2020.

114 citations

Journal ArticleDOI
TL;DR: A comprehensive integrative overview of the pleiotropic mechanisms, the metabolic pathways, and the inter-organ crosstalk involved in energy expenditure, fat mass loss, reduced inflammation, and healthy weight induced by exercise is emphasized.
Abstract: Exercise is an effective strategy for preventing and treating obesity and its related cardiometabolic disorders, resulting in significant loss of body fat mass, white adipose tissue browning, redistribution of energy substrates, optimization of global energy expenditure, enhancement of hypothalamic circuits that control appetite-satiety and energy expenditure, and decreased systemic inflammation and insulin resistance Novel exercise-inducible soluble factors, including myokines, hepatokines, and osteokines, and immune cytokines and adipokines are hypothesized to play an important role in the body's response to exercise To our knowledge, no review has provided a comprehensive integrative overview of these novel molecular players and the mechanisms involved in the redistribution of metabolic fuel during and after exercise, the loss of weight and fat mass, and reduced inflammation In this review, we explain the potential role of these exercise-inducible factors, namely myokines, such as irisin, IL-6, IL-15, METRNL, BAIBA, and myostatin, and hepatokines, in particular selenoprotein P, fetuin A, FGF21, ANGPTL4, and follistatin We also describe the function of osteokines, specifically osteocalcin, and of adipokines such as leptin, adiponectin, and resistin We also emphasize an integrative overview of the pleiotropic mechanisms, the metabolic pathways, and the inter-organ crosstalk involved in energy expenditure, fat mass loss, reduced inflammation, and healthy weight induced by exercise

99 citations

Journal ArticleDOI
TL;DR: This review focuses on myostatin, β‐aminoisobutyric acid, interleukin‐15, meteorin‐like and myonectin, and discusses how these myokines are induced and regulated as well as their overall function, and how they may be attractive therapeutic targets for treating muscle and metabolic diseases.
Abstract: Myokines are molecules produced and secreted by skeletal muscle to act in an auto-, para- and endocrine manner to alter physiological function of target tissues. The growing number of effects of myokines on metabolism of distant tissues provides a compelling case for crosstalk between skeletal muscle and other tissues and organs to regulate metabolic homoeostasis. In this review, we summarize and discuss the current knowledge regarding the impact on metabolism of several canonical and recently identified myokines. We focus specifically on myostatin, β-aminoisobutyric acid, interleukin-15, meteorin-like and myonectin, and discuss how these myokines are induced and regulated as well as their overall function. We also review how these myokines may serve as potential prognostic biomarkers that reflect whole-body metabolism and how they may be attractive therapeutic targets for treating muscle and metabolic diseases.

61 citations

Journal ArticleDOI
TL;DR: In this article , the authors combine an evolutionary perspective with physiological data to propose that interleukin 6's context-dependent effects on metabolism reflect its adaptive role for short-term energy allocation.
Abstract: Extensive research has shown that interleukin 6 (IL-6) is a multifunctional molecule that is both proinflammatory and anti-inflammatory, depending on the context. Here, we combine an evolutionary perspective with physiological data to propose that IL-6's context-dependent effects on metabolism reflect its adaptive role for short-term energy allocation. This energy-allocation role is especially salient during physical activity, when skeletal muscle releases large amounts of IL-6. We predict that during bouts of physical activity, myokine IL-6 fulfills the three main characteristics of a short-term energy allocator: it is secreted from muscle in response to an energy deficit, it liberates somatic energy through lipolysis and it enhances muscular energy uptake and transiently downregulates immune function. We then extend this model of energy allocation beyond myokine IL-6 to reinterpret the roles that IL-6 plays in chronic inflammation, as well as during COVID-19-associated hyperinflammation and multiorgan failure.

59 citations