Biology subjects

Chabert, C.

Publications and source records attributed to Chabert, C..

7 recordsLinked to original sources

bioRxiv2026

Distinct patterns of skeletal muscle wasting and mitochondrial changes following hypoxia and inflammation: associations with physiological phenotype

Skeletal muscle demonstrates a high degree of plasticity that may enable mitochondrial and protein turnover adaptations to environmental stressors such as hypoxia and inflammation. However, the effects of these stressors on skeletal muscle mitochondrial function and proteostatic pathways remain incompletely understood and may depend on muscle phenotype. Given the potential heterogeneity in skeletal muscle responses to these stressors, this study investigated their independent and combined effects on mitochondrial function and protein turnover pathways in oxidative soleus and glycolytic plantaris and assessed the consistency of these responses by comparison with a previous cohort. Adult male Wistar rats were exposed for four weeks to normobaric hypoxia and/or lipopolysaccharide-induced pulmonary inflammation. Mitochondrial respiration, enzymatic activities, markers of mitochondrial function and protein turnover and spontaneous locomotor activity (SLA) were assessed. Pulmonary inflammation predominantly affected soleus, triggering atrophy alongside impaired CI-dependent mitochondrial function, without changes in mitochondrial density. In contrast, plantaris exhibited only atrophy with no mitochondrial alterations in response to inflammation. Hypoxia induced atrophy selectively in plantaris. Notably, the changes following exposure to inflammation and/or hypoxia occurred independently of SLA alterations while the combination of these two stressors did not produce additive effects for most parameters. Comparison with our previous cohort revealed divergent responses that may have been influenced by differences in several physiological characteristics between the two cohorts. These findings demonstrate that hypoxia and pulmonary inflammation induce muscle-specific adaptations and suggest that physiological heterogeneity may contribute to variability in skeletal muscle vulnerability to chronic stress.

physiology↗

bioRxiv2026

Metabolic Heterogeneity of Muscle Stem Cells is Controlled by the Myofiber Niche

Metabolic pathways support biomass synthesis and provide substrates for epigenetic modifications of histones and DNA. These findings are particularly relevant for adult stem cells, where metabolic changes significantly impact functional behavior. However, assessing the metabolism of these cells in their native microenvironment is challenging as this typically necessitates dissociation prior to metabolic analysis. In this study, we focus on muscle stem cells (MuSCs) and show that removing these cells from the niche significantly alters their metabolic profile. To overcome this issue, we developed a novel enzymatic staining method for in situ metabolic profiling at a single-cell resolution. This approach reveals unexpected metabolic heterogeneity of MuSCs, identifying oxidative and glycolytic subsets, and demonstrates that their metabolism is directly modulated by adjacent myofibers. Accordingly, perturbing myofiber metabolism remodels the MuSC niche and drives metabolic adaptation in MuSCs. Finally, we define the kinetics by which myofiber-dependent metabolic regulation of MuSCs is re-established during muscle regeneration, thereby revealing how niche-imposed metabolic cues shape stem cell identity in vivo.

physiology↗

bioRxiv2025

Skeletal muscle fibre type determines mitochondrial and metabolic responses to hypoxia and pulmonary inflammation.

BackgroundChronic obstructive pulmonary disease (COPD) patients often experience skeletal muscle dysfunction that may result from a complex combination of mitochondrial dysfunction, metabolic reprogramming and fibre type transitions. Among other factors, pulmonary inflammation and hypoxia contribute to the COPD-associated muscle defects. Nevertheless, the precise molecular mechanisms and their effects across muscles with distinct metabolic profiles remain elusive. This study investigated the independent and combined effects of chronic pulmonary inflammation and chronic hypoxia on mitochondrial function, metabolic enzyme activity and fibre type composition in oxidative (soleus) and glycolytic (plantaris) muscles. MethodsAdult male Wistar rats were subjected to chronic hypoxia (FiO2=10%) and/or chronic pulmonary inflammation (induced by bi-weekly intratracheal instillations of lipopolysaccharides). After 4 weeks of exposure, mitochondria from both soleus and plantaris were isolated to measure oxygen consumption rates, reactive oxygen species (ROS) emission, calcium retention capacity (CRC), respiratory complex activities and fatty acid oxidation capacity. Cross-sections from both muscles were analysed for fibre typology, fibre cross-sectional area (fCSA) as well as succinate dehydrogenase (SDH) and glycerol-3-phosphate dehydrogenase (GPDH) activities. ResultsChronic hypoxia led to a decline in adenosine diphosphate-stimulated complex I (CI) respiration (p<0.01), Hydroxyacyl-Coenzyme A dehydrogenase activity (p<0.01), weight (p<0.05) and fCSA of type IIb fibres (p < 0.05) in plantaris. In contrast, chronic hypoxia increased CI-derived ROS emission (p<0.01) without changes in mitochondrial respiration or mass of soleus. No alterations in fibre typology were noticed in either muscle following the hypoxic exposure. Chronic pulmonary inflammation caused a reduction in mitochondrial CRC and an increase in GPDH activity in type IIa fibres of soleus (p<0.001) without any changes in fibre type distribution. Conversely, chronic pulmonary inflammation induced a downregulation of GPDH activity in plantaris type I and type IIa fibres, in parallel with an elevation in the SDH/GPDH ratio across all fibre types and a rise in the proportion of type IIx fibres. ConclusionsOur results demonstrate fundamental differences in the responses to chronic hypoxia and chronic pulmonary inflammation between soleus and plantaris. While hypoxia affects predominantly the mitochondrial function and mass of plantaris, pulmonary inflammation drives metabolic reprogramming in both muscles that opposes their intrinsic functional specialisation. Additionally, soleus appears more vulnerable to permeability transition pore opening following pulmonary inflammation. Notably, these mitochondrial alterations seem to occur independently of fibre type shifts highlighting the central role of intrinsic mitochondrial maladaptations in the COPD-associated muscle dysfunction.

physiology↗

bioRxiv2025

Transcriptomic analysis of chronic chikungunya in the Reunionese CHIKGene cohort uncovers a shift in gene expression more than 10 years after infection

AimIn 2005-2006, a chikungunya epidemic of unprecedented magnitude hit Reunion Island, which raised a public health concern through the substantial proportions of long-lasting manifestations. To understand the pathophysiology underlying chronic chikungunya (CC), we designed the CHIKGene cohort study and collected blood samples from 133 subjects diagnosed with CC and from 86 control individuals that had recovered within 3 months, 12-to-15 years after exposure. MethodsWe conducted bulk RNAseq analysis on peripheral blood mononuclear cells to find differentially expressed genes (DEGs), gene set enrichment analysis (GSEA) and gene ontologies to uncover top-level enriched terms associated with DEGs, and weighted gene correlation network analysis (WGCNA) to elucidate underlying cellular processes. ResultsAmong 1549 DEGs, gene expression analysis identified 10 top genes including NR4A2 and TRIM58 (upregulated in CC), IGHG3 and IGHV3-49 (downregulated in CC) linked to immune regulation, OSBP2 (upregulated in CC) and SEMA6B (downregulated in CC) linked to neuronal homeostasis and axon guidance, respectively. GSEA and WGCNA unveiled cellular processes such as "Metabolism of RNA" and "Cell Cycle". ConclusionsThis study uncovers a shift in gene expression of CC subjects. IGHG3 and IGHV3-49 gene shut-offs spotlight the importance of neutralizing antibodies against chikungunya virus in the progression to chronic disease. Human diseases associations highlight connections to rheumatoid arthritis, nervous and cardiac systems. GSEA and WGCNA bounce the hypotheses of a persistent viral reservoir or an increased susceptibility to RNA viral pathogens with new onset infections. Together, our findings might offer potential targets for therapeutic options aimed at alleviating chronic chikungunya.

bioinformatics↗

bioRxiv2021

Paper-and-pencil questionnaires analysis: a new automated technique to reduce analysis time and errors.

Background and ObjectiveQuestionnaires are essential tools in many scientific fields, including health and medicine. However, the analysis of paper-and-pencil questionnaires is time consuming, source of errors and expensive, limiting its use in large cohort studies. Computer-based questionnaires might be a valuable alternative but they may introduce bias, especially for sensitive questions, and they require programming skills. The aim of this study is to develop a reliable and adaptable open-source technique (i.e. LightQuest) to automatically analyse various types of scanned paper-and-pencil questionnaires with closed questions, including those with inverted scale. MethodsTo evaluate the usefulness of LightQuest, the time needed for 7 experimenters for manually code 10 sets of 4 frequently used questionnaires and the number of errors (i.e. reliability) were compared with the time and errors their made using LightQuest. ResultsLightQuest was twice as fast as the manual analysis, even though the time to create the reference model was taken into account (933s vs. 1935s, t(2)=8.81, p<0.001). Without model creation, the reduced analysis time was more pronounced, with an average of 2.77s.question-1 for the manual technique versus 0.55s.question-1 for LightQuest (t(2)=22.5, p<0.001). Moreover, during correction of the 5180 questions performed by the 7 experimenters, LightQuest made a total of 2 errors versus 46 with the manual technique (q(2)=4.53, p<0.05). ConclusionLightQuest demonstrated clear superiority both in terms of time and reliability. The script of this first open-source technique, which does not require programming skills, is downloadable in supplemental data and may become an asset for all studies using questionnaires.

scientific communication and education↗

bioRxiv2020

Validity of dynamical analysis to characterize heart rate and oxygen consumption during effort tests

Performance is usually assessed by simple indices stemming from cardiac and respiratory data measured during graded exercise test. The goal of this study is to test the interest of using a dynamical analysis of these data. Therefore, two groups of 32 and 14 athletes from two different cohorts performed two different graded exercise testing before and after a period of training or deconditioning. Heart rate (HR) and oxygen consumption (VO2) were measured. The new dynamical indices were the value without effort, the characteristic time and the amplitude (gain) of the HR and VO2 response to the effort. The gain of HR was moderately to strongly associated with other performance indices, while the gain for VO2 increased with training and decreased with deconditioning with an effect size slightly higher than VO2 max. Dynamical analysis performed on the first 2/3 of the effort tests showed similar patterns than the analysis of the entire effort tests, which could be useful to assess individuals who cannot perform full effort tests. In conclusion, the dynamical analysis of HR and VO2 obtained during effort test, especially through the estimation of the gain, provides a good characterization of physical performance, robust to less stringent effort test conditions.

bioinformatics↗

bioRxiv2020

The complex relationship between effort and heart rate: a hint from dynamical analysis

Heart rate during effort test has been previously successfully adjusted with a simple first order differential equation with constant coefficients driven by the body power expenditure. Although producing proper estimation and yielding pertinent indices to analyze such measurement, this approach suffers from its inability to model the saturation of the heart rate increase at high power expenditure and the change of heart rate equilibrium after effort. The objective of the present study is to improve this model by considering that the amplitude of the heart rate response to effort (gain) depends on the power expenditure value. Therefore, heart rate and oxygen consumption of 30 amateur athletes were measured while they performed a maximum graded treadmill effort test. The proposed model was able to predict 99% of the measured heart rate variance during exercise. The gains estimated at the different power expenditures were constant but noisy before the first ventilatory threshold, stable and decreasing slightly with power increase between the two ventilatory thresholds, before decreasing in a more pronounced manner after the second ventilatory threshold. The slope of the decrease of heart rate gain with power expenditure was correlated with the deflection angle of the heart rate performance curve and with the maximum oxygen consumption. These results reflect the changes of metabolic energy systems at play during the effort test and are consistent with the analysis of the heart rate performance curve given by the Conconi method, thus validating our new approach to analyze heart rate during effort test.

bioinformatics↗