Marc Francaux

• PhD
• Professor (Full) at Catholic University of Louvain

Sickle cell disease (SCD) patients display skeletal muscle hypotrophy, altered oxidative capacity, exercise intolerance and poor quality of life. We previously demonstrated that moderate‐intensity endurance training is beneficial for improving muscle function and quality of life of patients. The present study evaluated the effects of this moderate‐...

Among patients with multiple sclerosis (MS), the impairment of exercise tolerance is closely related to disability. Maximal oxygen uptake (VO2max) is the gold standard to assess exercise tolerance in healthy subjects (HS). Among patients with MS, the accuracy of VO2max measurement is often impaired because the patients are unable to reach the maxim...

Pancreas ductal adenocarcinoma is one of the deadliest cancers where surgery remains the main survival factor. Mitochondria were described to be involved in tumor aggressiveness in several cancer types including pancreas cancer. We have previously reported that myoferlin controls mitochondrial structure and function, and demonstrated that myoferlin...

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) originated in China in late 2019 and has since spread rapidly to every continent in the world. This pandemic continues to cause widespread personal suffering, along with severe pressure on medical and health care providers. The symtoms of SARS‐CoV‐2 and the subsequent prognosis is worsene...

Over the last three decades, the combination of a sedentary lifestyle and excessive food intake has led to a significant increase in the prevalence of obesity. The latter favors a chronic low-grade inflammatory state and an over-activation of the innate immune system, which contribute to insulin resistance and type 2 diabetes. Physical exercise is...

Over the last three decades, the combination of a sedentary lifestyle and excessive food intake has led to a significant increase in the prevalence of obesity. The latter favors a chronic low-grade inflammatory state and an over-activation of the innate immune system, which contribute to insulin resistance and type 2 diabetes. Physical exercise is...

This study investigated whether regular endurance exercise maintains basal mitophagy and mitochondrial function during aging. Mitochondrial proteins and total mRNA were isolated from vastus lateralis biopsies (n = 33) of young sedentary (YS), old sedentary (OS), young active (YA), and old active (OA) men. Markers for mitophagy, fission, fusion, mit...

The preparation of long-distance runners requires to estimate their potential race performances beforehand. Athlete performances can be modeled based on their past records, but the task is made difficult because of the high variability in runner race performances. This paper presents a maximum a posteriori (MAP) estimation that addresses the issues...

During the course of life, muscle mass undergoes many changes in terms of quantity and quality. Skeletal muscle is a dynamic tissue able to hypertrophy or atrophy according to growth, ageing, physical activity, nutrition and health state. The purpose of the present review is to present the mechanisms by which exercise can induce changes in human sk...

Background: Skeletal muscle atrophy is a common feature of numerous chronic pathologies and is correlated with patient mortality. The REDD1 protein is currently recognized as a negative regulator of muscle mass through inhibition of the Akt/mTORC1 signaling pathway. REDD1 expression is notably induced following glucocorticoid secretion, which is a...

The aim of the study was to determine the effect of α-actinin-3 (ACTN3) deficiency (XX) on muscle damage induced by an eccentric exercise bout. In this purpose, 4 RR and 4 XX individuals performed an intensive eccentric knee flexion exercise on an isokinetic dynamometer. Muscle biopsies, blood and pain scores were taken before and after the exercis...

Objective Hypoxia is a state of lowered oxygen tension in tissue that can be created by environmental or pathological conditions. Whatever the origin of hypoxia, different tissues will adapt acutely and/or chronically to deal with this reduction in oxygen availability. Hypoxia has recently emerged as a particularly efficient stimulus to stimulate m...

Running routes' elevation profiles affect their runnability and therefore athletes' average speeds: route distances alone are not sufficient to predict or evaluate running times. This is an issue for race preparation, race strategy, performance comparison and runner workload planning anytime the ground is sloping. This paper proposes a methodology...

The purpose of this study was to analyze the pacing strategy and its affective consequences during self-paced cycling time trials (TT) performed at different severity of hypoxia. Eight competitive cyclists performed five 30 min self-paced TTs at their best performance in the following conditions: 1) normobaric normoxia (NNSL); 2) normobaric hypoxia...

Introduction/Background Measured maximal oxygen uptake (VO2peak) is the gold standard to assess exercise tolerance functions. However, this measure can be very challenging in patients suffering from multiple sclerosis (MS) because of several limiting factors (e.g., fatigue, pain, unfamiliarity with exercise, lack of mobility…). Various submaximal i...

Objectives: As the catabolic state induced by septic shock together with the physical inactivity of patients lead to the rapid loss of muscle mass and impaired function, the purpose of this study was to test whether an early physical therapy during the onset of septic shock regulates catabolic signals and preserves skeletal muscle mass. Design:...

We hypothesized that a single session of resistance exercise performed in moderate hypoxic (FiO2: 14%) environmental conditions would potentiate the anabolic response during the recovery period spent in normoxia. Twenty subjects performed a 1-leg knee extension session in normoxic or hypoxic conditions. Muscle biopsies were taken 15 min and 4 h aft...

Purpose of review: To highlight recent evidence for the ability of polyphenols and their derivatives to reduce muscle wasting in different pathological states. Recent findings: From January 2016 to August 2017, four articles dealt with the effects of polyphenols on muscle wasting, which were all carried out in mice. The four studies found that p...

Background: Obesity and metabolic syndrome are disorders that correlate with the activation of pro-inflammatory pathways and cytokine production, to which Toll like receptors (TLR) contribute. Exercise may act as an anti-inflammatory modulator, but there is no consensus about the role of the TLR in this tuning. The present styudy aims to systemati...

Introduction : La drépanocytose est une hémoglobinopathie génétique ayant pour conséquences deux manifestations cliniques majeures : une anémie hémolytique chronique sévère et des crises vaso-occlusives itératives. Récemment, nous avons mis en évidence que la drépanocytose s’accompagnait d’un remodelage profond du tissu musculaire, contribuant à l’...

Introduction : La drépanocytose est une hémoglobinopathie génétique ayant pour conséquences deux manifestations cliniques majeures : une anémie hémolytique chronique sévère et des crises vaso-occlusives itératives. Récemment, nous avons mis en évidence que la drépanocytose s’accompagnait d’un remodelage profond et délétère du tissu musculaire, cont...

Activating transcription factor (ATF) 3 regulates chemokine expression in various cell types and tissues. Herein, we studied this regulation in contracting muscle cells in vitro, and in skeletal muscle after muscle-damaging exercise in vivo. C2C12 myotubes with normal or low ATF3 levels (atf3_siRNA) were electrically stimulated (EPS). Also, ATF3-kn...

Figure S1. Effect of urolithins A and B on the size and effect of urolithin B on the energy status of C2C12 myotubes. (A and C) After four days of differentiation, C2C12 myotubes were treated with urolithin B, urolithin A or vehicle DMSO (CTRL) for additionally 24 h. Cells were then fixed and immunostained with anti‐desmin, nuclei were revealed by...

Figure S5. Signaling associated with reduction of muscle atrophy by urolithin B in mice. (A‐F) Representative immunoblots and quantification for total FoxO3a or phosphorylated FoxO1/?FoxO3a normalized to GAPDH expression, for the ratio of phosphorylated Akt on total Akt, for the ratio of phosphorylated AMPK on total AMPK, for the ratio of phosphory...

Figure S3. Positive and negative controls supporting the implication of the androgen receptor in enhancement of myotube growth induced by urolithin B. (A‐C) The androgen receptor (AR) was inactivated in C2C12 myotubes by siRNA targeting the receptor (siRNA AR). (A) mRNA level of AR in cells transfected with a scramble (Scr) or siRNA, and treated or...

Figure S4. Urolithin B increases puromycin incorporation in soleus muscle. (A) Representative image of WB analysis for puromycin, from SOL protein samples. (B) Quantification of the puromycin‐labeled peptides in SOL muscle, expressed as a percentage of the values obtained in the control group. Data are means ± SEM from 6 mice per condition. P‐value...

Supplemental Experimental Procedures

Figure S2. Urolithin B does not regulate autophagy in C2C12 myotubes. (A) Quantification and representative immunoblots of the ULK1 phosphorylation state at Ser757 and (B) the ratio LCBII/?LC3BI. (C) Effect of urolithin B on Lc3b, p62 and Gabarapl‐1 mRNA levels, normalized to RPL‐19 mRNA, as assessed by qPCR. Incubation conditions: urolithin B (Uro...

Skeletal muscle mass reflects a dynamic turnover between net protein synthesis and degradation. In addition, satellite cell inclusion may contribute to increase muscle mass while fiber loss results in a reduction of muscle mass. Since 2010, a few studies looked at the involvement of the newly discovered Hippo pathway in the regulation of muscle mas...

Background: The control of muscle size is an essential feature of health. Indeed, skeletal muscle atrophy leads to reduced strength, poor quality of life, and metabolic disturbances. Consequently, strategies aiming to attenuate muscle wasting and to promote muscle growth during various (pathological) physiological states like sarcopenia, immobiliz...

Purpose: To determine whether fission and mitophagy are activated by acute endurance exercise in human skeletal muscle and to investigate if this activation is dependent upon the nutritional state. Methods: Trained athletes (n = 7) cycled for 2 h at 70% VO2 peak in a fed or fasted state. Vastus lateralis muscle biopsies were obtained at baseline...

This work provides tools based on matrix factorization that can be used to predict athlete running race times based on known race results. This is of interest for athlete preparation, for workout route planning and for race events organization. This work differentiates from previous ones by jointly considering athletes and routes. This work shows h...

Activating transcription factor (ATF)3 regulates the expression of inflammation-related genes in several tissues under pathological contexts. In skeletal muscle, atf3 expression increases after exercise, but its target genes remain unknown. We aimed to identify those genes and to determine the influence of ATF3 on muscle adaptation to training. Ske...

Scope: We investigated whether punicalagin-rich pomegranate extract (PE) protects skeletal muscle of mice against inflammation induced by an acute injection of TNF-α. Results: Mice fed with PE or standard chow during six weeks were injected with TNF-α (100 ng/g) or vehicle and sacrificed six hours later. Prior supplementation with PE prevented t...

Assessment of physical fitness of endurance athletes is usually performed by means of standardized exercise protocols in specialized laboratories. The recent development of devices measuring heart rate, power output, speed, etc. raises the possibility to assess the fitness level from data collected on the field. We propose a model based on cardiac...

Introduction et but de l’étude Le muscle squelettique est le tissu le plus abondant du corps humain. Le contrôle de sa masse est essentiel pour assurer ses fonctions physiologiques comme la locomotion, la respiration ou encore la posture. Il joue également un rôle majeur dans le contrôle du métabolisme. L’atrophie musculaire est associée à une dimi...

Purpose of review: The purpose of this article is to collect the most recent data regarding the safety of well-known or emerging dietary supplements used by athletes. Recent findings: From January 2014 to April 2016, about 30 articles have been published in the field. New data show that 90% of sports supplements contain trace of estrogenic endoc...

DNA breaks activate the DNA damage response and, if left unrepaired, trigger cellular senescence. Telomeres are specialized nucleoprotein structures that protect chromosome ends from persistent DNA damage response activation. Whether protection can be enhanced to counteract the age-dependent decline in telomere integrity is a challenging question....

Purpose: To examine the effect of α-actinin-3 deficiency due to homozygosity for the ACTN3 577X-allele on contractile and morphological properties of fast muscle fibers in non-athletic young men. Methods: A biopsy was taken from the vastus lateralis of 4 RR and 4 XX individuals to test for differences in morphologic and contractile properties of...

Chronic hypoxia leads to muscle atrophy. The molecular mechanisms responsible for this phenomenon are not well defined in vivo. We sought to determine how chronic hypoxia regulates molecular markers of protein synthesis and degradation in human skeletal muscle and whether these regulations were related to the regulation of the hypoxia-inducible fac...

Properties of single muscle fibers with mixed MHC-isoforms in participants with RR and XX genotypes. Values are means±SE. n.a. = not applicable. (DOCX)

This study was designed to better understand the molecular mechanisms involved in the anabolic resistance observed in elderly people. Nine young (22 ± 0.1 years) and 10 older (69 ± 1.7 years) volunteers performed a one-leg extension exercise consisting of 10 × 10 repetitions at 70% of their 3-RM, immediately after which they ingested 30 g of whey p...

Regular physical exercise is widely recognized as a primary prevention tool to fight against many chronic diseases. The transitory activation of autophagy by endurance exercise has recently emerged as a homeostatic mechanism contributing to exercise-mediated health benefits. Studies performed both in mice and human muscle after running exercise sho...

Anabolic resistance reflects the inability of skeletal muscle to maintain protein mass by appropriate stimulation of protein synthesis. We hypothesized that endoplasmic reticulum (ER) stress contributes to anabolic resistance in skeletal muscle with aging. Muscles were isolated from adult (8 mo) and old (26 mo) mice and weighed. ER stress markers i...

Endoplasmic reticulum (ER) stress is a central actor in the physiopathology of insulin resistance (IR) in various tissues. The subsequent unfolded protein response (UPR) interacts with insulin signaling through inositol-requiring 1α (IRE1α) activation and tribbles homolog 3 (TRB3) expressions. IRE1α impairs insulin actions through the activation of...

To determine whether endurance training attenuates the negative effects induced by an acute injection of tumor necrosis factor-α (TNF-α) in skeletal muscle of mice. Trained (6 weeks of endurance training at 60% of maximal velocity) and untrained mice were injected with TNF-α or vehicle and sacrificed six hours after. Tibialis anterior muscles were...

Chronic hypoxia substantially decreases skeletal muscle in physiological and pathological states. We sought to determine how chronic hypoxia regulates Hypoxia-Inducible-Factors (HIF-1α and HIF-2α) and if these regulate mTORC1 and autophagy in human skeletal muscle. Eight young male subjects lived in a hypoxic hotel for 15 days at FiO2: 14.1%. Nutr...

The purpose of this review is to present the basic principles of a healthy nutrition in female endurance runner enriched by the latest scientific recommendations. Female endurance runners are a specific population of athletes who need to take specifically care of daily nutrition due to the high load of training and the necessity to keep a rather lo...

In humans, nutrient deprivation and extreme endurance exercise both activate autophagy. We hypothesized that cumulating fasting and cycling exercise would potentiate activation of autophagy in skeletal muscle. Well-trained athletes were divided into control (n = 8), low-intensity (LI, n = 8), and high-intensity (HI, n = 7) exercise groups and submi...

Background The ubiquitin-proteasome pathway (UPP) is a major protein degradation pathway that is activated during sepsis and has been proposed as a therapeutic target for preventing skeletal muscle loss due to cachexia. Although several studies have investigated the modulation of proteasome activity in response to LPS administration, none have char...

Purpose: We tested the hypothesis that polyphenol-rich extracts can reduce endoplasmic reticulum (ER) stress induced by a high-fat diet (HFD) in skeletal muscle of mice. Methods: Mice were randomly assigned to four groups receiving during 20 weeks either a standard chow control (CTRL), or a HFD supplemented, or not, with pomegranate (HFD + P) or...

Activation of autophagy in skeletal muscle has been reported in response to endurance exercise and food deprivation, independently. The purpose of this study was to evaluate whether autophagy was more activated when both stimuli were combined, namely when endurance exercise was performed in a fasted rather than a fed state. Mice performed a low int...

The purpose of this study was to investigate whether toll-like receptor 4 (TLR4) is implicated in the development of endoplasmic reticulum stress (ER stress) observed after a high-fat diet (HFD) in liver, skeletal muscle and adipose tissue. TLR4(-/-) and C57BL/6J wild-type mice (WT) were fed with chow or HFD (45% calories from fat) during 18 weeks....

Objective The purpose of this study was to validate a French version of the Decisional Balance Scale for Exercise (BDAP) and to examine its psychometric properties as well as its relationship with the three other components of Transtheoritical Model (TTM).Participants and methodFour hundred and six subjects (270 women), aged between 16 to 65 years...

Hypoxia-induced muscle wasting has been observed in several environmental and pathological conditions. However, the molecular mechanisms behind this loss of muscle mass are far from being completely elucidated, certainly in vivo. When studying the regulation of muscle mass by environmental hypoxia, many confounding factors have to be taken into acc...

Objective The purpose of the present study is to validate a French version of Exercise Processes of Change Questionnaire (PCQ) and to examine its psychometric properties and its relation with the other components of Transtheoritical Model (TTM). Methods Two hundred ninety-three subjects (198 women), 16–65 years old, answered the PCQ and other ques...

A common nonsense polymorphism in the ACTN3 gene results in the absence of α-actinin-3 in XX individuals. The wild type allele has been associated with power athlete status and an increased force output in numeral studies, though the mechanisms by which these effects occur are unclear. Recent findings in the Actn3(-/-) (KO) mouse suggest a shift to...

Mitogen-activated protein kinase (MAPK) pathways are activated in skeletal muscle during endurance exercise, but the upstream molecular events are incompletely resolved. As an increase in plasma non-esterified fatty acids (NEFA) is a common feature of long-lasting exercise, we tested the hypothesis that NEFA contribute to the activation of MAPK dur...

Toll-like receptors 2 (TLR2) and 4 (TLR4) are present in the plasma membrane of skeletal muscle cells where their functions remain incompletely resolved. They are able to bind various extra-cellular ligands, such as FSL-1, lipopolysaccharide (LPS) and/or palmitic acid (PA). The purpose of this study was to investigate the link between PA, TLR2/4, a...

Certain conditions, such as several weeks of high-fat diet, disrupt endoplasmic reticulum (ER) homeostasis and activate an adaptive pathway referred as the unfolded protein response. When the unfolded protein response fails, the result is the development of inflammation and insulin resistance. These two pathological states are known to be improved...

In this study, the coordinated activation of ubiquitin-proteasome pathway (UPP), autophagy-lysosomal pathway (ALP), and mitochondrial remodeling including mitophagy was assessed by measuring protein markers during ultra-endurance running exercise in human skeletal muscle. Eleven male, experienced ultra-endurance athletes ran for 24 h on a treadmill...

Toll-like receptors 2 and 4 (TLR2, TLR4) are found in the membrane of skeletal muscle cells. A variety of molecular components can activate TLR2 and TLR4, among others, long-chain fatty acids. The subsequent downstream signaling triggers the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways. Therefore, the purpose of th...

Le questionnaire Exercise Confidence Survey mesure l'auto-efficacité perçue pour la pratique d'une activité physique régulière. Sallis (1996) a identifié deux dimensions dans l'Exercise Confidence Survey: l'adhésion à l'activité physique (sticking to it) et le temps consacré à l'activité physique (making time for exercise). L'objectif de la présent...

The purpose of this study was to evaluate whether ultra endurance exercise changes the mRNA levels of the autophagy-related and autophagy-regulatory genes. Eight men (44 ± 1 years, range: 38-50 years) took part in a 200-km running race. The average running time was 28 h 03 min ± 2 h 01 min (range: 22 h 15 min-35 h 04 min). A muscle sample was taken...

In secretory organs, such as the liver, the pancreas, and the adipose tissue, endoplasmic reticulum (ER) stress plays a key role in the etiology of cell disturbances implicated in many diseases. Although much less studied, ER stress also is present in skeletal muscle. In the present review, we hypothesize that ER stress may have important metabolic...

Genes significantly modulated in the liver of n-3 PUFA depleted mice (DEF) compared to control mice (CT). Genes significantly up (positive values) or downregulated (negative values) in the liver of mice fed with an n-3 PUFA depleted (DEF) diet for three months compared to mice fed with a control (CT) diet in the fasted and fed state. Results are ob...

Transcription factor predictions by TFactS. The list of genes changed in n-3 PUFA depleted mice compared to control mice (in the fed and starved conditions) was submitted to TFactS (sign-less) using default settings. Transcription factors that are significantly regulated with P-value, E-value, Q-value, FDR and random control <5% are shown. The regu...

qPCR confirmation of genes modulated in the liver of n-3 PUFA depleted mice (DEF) compared to control mice (CT). mRNA content of sterol-regulatory-element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), ATP-binding cassette transporters G5 (ABCG5), insulin induced gene 2a (Insig2a), carbohydrate-responsi...

Primers sequences used for real-time quantitative PCR. RPL19; ribosomal protein L19, FAS; fatty acid synthase, SREBP-1c; sterol-regulatory-element-binding protein-1c, Chrebp; carbohydrate-responsive element-binding protein, L-PK; liver-pyruvate kinase, SCD-1; stearoyl-CoA desaturase-1, ATP-binding cassette transporters G5; ABCG5, cyp7a1; cytochrome...

Endocannabinoids content in the liver of CT and DEF mice. 2-arachidonoylglycerol (nmol/g liver tissue), N-arachidonoylethanolamine (pmol/g liver tissue), N-palmitoylethanolamine (pmol/g liver tissue), N-stearoylethanolamine (pmol/g liver tissue) and N-oleoylethanolamine (pmol/g liver tissue) content in the liver of fasted mice fed with a control (C...

Pathway and gene ontology analysis using DAVID. The consensus list of regulated genes was submitted to DAVID. Terms that were significantly represented (corrected P-values and FDR <0.05) are shown. Redundant terms were removed. (DOC)

Composition of control (CT) and n-3 PUFA depleted (DEF) diet. Formulated by Research Diets. Parenthetical numbers indicate the manufacturer's diet number. (DOC)

Fatty acid composition of soybean and sunflower oil. Fatty acid composition of soybean and sunflower oil used for the CT and DEF diet respectively. (DOC)

Patients with non-alcoholic fatty liver disease are characterised by a decreased n-3/n-6 polyunsaturated fatty acid (PUFA) ratio in hepatic phospholipids. The metabolic consequences of n-3 PUFA depletion in the liver are poorly understood. We have reproduced a drastic drop in n-3 PUFA among hepatic phospholipids by feeding C57Bl/6J mice for 3 month...

Anabolic resistance is the inability to increase protein synthesis in response to an increase in amino acids following a meal. One potential mediator of anabolic resistance is endoplasmic reticulum (ER) stress. The purpose of the present study was to test whether ER stress impairs the response to growth factors and leucine in muscle cells. Muscle c...

Our goal was to determine whether in vivo administration of the proteasome inhibitor MG132 can prevent muscle atrophy caused by hindlimb unloading (HU). Twenty-seven NMRI mice were assigned to a weight-bearing control, a 6-day HU, or a HU+MG132 (1 mg/kg/48 h) treatment group. Gastrocnemius wasting was significantly less in HU+MG132 mice (-6.7 ± 2.0...

This study investigated whether a 200-km run modulates signaling pathways implicated in cellular stress in skeletal muscle, with special attention paid to the endoplasmic reticulum (ER) stress and to the activation of the ubiquitin-proteasome pathway. Eight men ran 200 km (28 h 03 min ± 2 h 01 min). Two muscle biopsies were obtained from the vastus...

Endoplasmic reticulum (ER) stress in pancreas, liver, and adipose tissue is a key event in the pathogenesis of obesity-related metabolic disease. Lipid-induced ER stress in liver and adipose tissue leads to inhibition of insulin signaling. Whether this mechanism exists in skeletal muscle is currently unknown. The present study aimed at assessing th...

High-fat diets are known to decrease muscle protein synthesis, the adaptation to overload, and insulin sensitivity. Conditions that disrupt endoplasmic reticulum (ER) homeostasis lead to the activation of the unfolded protein response (UPR) that is associated with decreases in protein synthesis, chronic inflammation, and insulin resistance. The pur...

Inulin-type fructans (ITF) are nondigestible/fermentable carbohydrates which are able - through the modification of the gut microbiota - to counteract high-fat (HF) diet-induced obesity, endotoxemia and related-metabolic alterations. However, their influence on adipose tissue metabolism has been poorly studied until now. The aim of this study was t...

Introduction Les acides gras polyinsaturés (AGPI) n-3 jouent un rôle important sur le métabolisme lipidique de part leur capacité à stimuler la β-oxydation et à diminuer la lipogenèse. Une augmentation du ratio n-6/n-3 est observée dans les phospholipides du foie de patientes atteintes de stéatose hépatique non alcoolique. L’implication d’une dimin...

Une diète hyperlipidique provoque une accumulation de masse grasse et une modification de la composition du microbiote intestinal. L’administration de prébiotiques fermentés par certaines bactéries saccharolytiques permet de contrer l’obésité et les altérations métaboliques induites par la diète. Deux récepteurs couplés aux protéines G et liant les...

Magnesium (Mg) deficiency is a common nutritional disorder that is linked to an inflammatory state characterized by increased plasma acute phase protein and proinflammatory cytokine concentrations. Recent studies have shown that changes in the composition of gut microbiota composition participate in systemic inflammation. In this study, therefore,...