Biology subjects

Caron, A.

Publications and source records attributed to Caron, A..

12 recordsLinked to original sources

bioRxiv2026

Dietary protein source dictates the impact of obesogenic diets on hepatic steatosis and insulin resistance via carnitine-dependent regulation of acetyl-CoA carboxylase

Nutritional strategies to mitigate obesity and type 2 diabetes (T2D) have largely focused on dietary fat and carbohydrate composition, with less attention given to protein sources. While total dietary protein intake is recognized as an important modulator of energy balance and glucose metabolism, it remains unclear how the composition of dietary proteins can influence energy metabolism and body weight gain. Here, we investigated the metabolic effects of three distinct protein sources from meat (pork), dairy (casein) and plant (soy) on either a low-fat low sucrose (LFLS) or a high-fat high sucrose (HFHS) diet. While protein sources failed to influence metabolic homeostasis on LFLS, mice kept on the HFHS diet were distinctly impacted by the dietary protein sources. Pork and to a lesser extent soy protein feeding exacerbated obesity, glucose intolerance, and hepatic insulin resistance. Remarkably, livers of mice fed pork or soy protein on the HFHS diet were characterized by extensive microvesicular steatosis compared to the predominant macrovesicular steatosis in HFHS fed mice fed casein protein. Liver transcriptomic and metabolomic signatures in pork and soy protein fed mice were consistent with increased mitochondrial beta-oxidation. Intake of pork and soy proteins in HFHS fed mice lead to a striking reduction in hepatic acetyl CoA carboxylase 2 (ACC2) protein levels relative to casein fed HFHS mice. Pork and soy feeding raised carnitine exposure in the post-prandial period and we determined that exposure of hepatocytes to carnitine provokes downregulation of ACC2 and hepatic insulin resistance in the presence of palmitate:oleate and fructose. Collectively, these findings identify a novel mechanism by which dietary proteins modulate obesity and associated metabolic disturbances through a carnitine-mediated regulation of ACC2 protein and mitochondrial lipid handling in liver. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/732886v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@1cc5b9corg.highwire.dtl.DTLVardef@1929e43org.highwire.dtl.DTLVardef@d453faorg.highwire.dtl.DTLVardef@1d56149_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2025

Using social network analysis and non-invasive antibody detection to explore pathogen exposure in wildlife communities

Understanding the dynamics of infectious diseases in ecosystems shared with wildlife is a priority for preventing future threats to human, animal health and conservation. However, the collection of ecological and epidemiological data on wild populations has relied on invasive and costly methods which limited the capacity of investigation. Recent technological developments have changed this trend. In Hwange national park and its surrounding area in Zimbabwe, we combined camera trap-based ecological monitoring over a period of 12 months, covering 14 water holes with a fecal-based antibody survey in 16 large herbivore species. A survey involving 52,829 pictures as well as 629 faecal samples collected every 15 days, has shown Through the modelling of multispecies contact networks, the risk of infection exposure at species-level is predicted. Coupled with foot-and-mouth disease virus (FMDV) antibody information, the role of each species in the dynamics of infectious diseases is explored. This study highlights how community networks can provide valuable insights into the functional epidemiological role of wildlife populations. Rather than establishing transmission routes, our aim is to propose a scalable and non-invasive surveillance framework that identifies priority species and areas for epidemiological monitoring in complex ecological systems. Significance StatementMonitoring disease circulation in wildlife is often hindered by the difficulty of collecting epidemiological data. We propose a novel non-invasive approach that combines species interaction networks derived from camera-trap data with non-invasive antibody detection to explore the exposure patterns of large herbivore communities to foot-and-mouth disease virus (FMDV). By linking the position of species in contact networks with their immunological status, we demonstrate the potential of using ecological centrality as a proxy for identifying key hosts in transmission or indicator species for pathogen circulation. Beyond FMDV, this framework can be adapted to other pathogens for which non-invasive immunological assays are currently being developed, making it broadly relevant for wildlife disease surveillance in remote or protected areas.

ecology↗

bioRxiv2025

Combining artificial intelligence and local ecological knowledge to document the largest ever-counted Cape buffalo mega-herd

Large aggregations of wild mammals are declining globally, sometimes before they can be scientifically documented and their ecological value understood, although non-scientists may be aware of these phenomena. Video recording of wildlife by non-academics is becoming more frequent with increasing activities of humans in natural habitats. This opportunistically-collected material can document rare or ecologically-important events, such as large aggregations, and thus provide potentially valuable data for ecologists and conservationists. We used footage of a large herd of Cape buffalo recorded by a wildlife film producer in the Mababe Depression, northern Botswana, and applied automated detection and tracking techniques to count individuals as they moved across the video frame. To complement this demographic snapshot, we accessed local ecological knowledge from stakeholders to provide contextual information for a more complete understanding of the ecosystem processes potentially driving population movement and trends. Manual review of the automated count resulted in a minimum group size of 3676 buffalo and a total estimated herd size of 4131 (range 3828-4446), which matched herd size estimates provided by local stakeholders. To our knowledge, this is the largest documented group of Cape buffalo, which we identify as a mega-herd and recommend research into the costs, benefits and ecological consequences of forming such large groups. This study represents an opportunistic collaboration among wildlife filmmakers, computer scientists, lay experts and ecologists, and highlights the value of combining contributions from different fields to generate information that can be used in conservation practice.

ecology↗

bioRxiv2025

Integration of Multiomic and Multi-phenotypic Data Identifies Biological Pathways Associated with Physical Fitness

Unraveling the complex associations between human phenotypes and molecular pathways can pave the way to improved health and performance, but faces a fundamental challenge: the measurable genes, proteins, and metabolites vastly outnumber the participants in even the largest studies, yielding spurious correlations. To address this imbalance, we have developed a bioinformatic framework and computational approach ("PhenoMol") to discover biological drivers of phenotypic characteristics that integrates all available phenotypic data predictive of outcomes and reduces multi-omic data dimensionality by generating "expression circuits" via graph theory constrained by prior biological knowledge of molecular interactions. We applied PhenoMol to analyze causal patterns and predict elite physical performance in a healthy cohort with deep physiological, physical, behavioral, cognitive, and molecular characterization. PhenoMol outperforms regression models based on equivalent analytic methodologies that do not employ network biology for dimensionality reduction. The PhenoMol software is provided for future studies.

bioinformatics↗

bioRxiv2025

Deep-mutational scanning libraries using tiled-region exchange mutagenesis

The analysis of gene function frequently requires the generation of mutants. Deep-mutational scanning (DMS) has emerged as a powerful tool to decipher important functional residues within genes and proteins. However, methods for performing DMS tend to be complex or laborious. Here, we introduce Tiled-Region Exchange (T-REx) Mutagenesis, which is a multiplexed modification of the EMPIRIC mutagenesis approach. Self-encoded removal fragments are cloned in parallel in non-overlapping gene locations and pooled. In a one-pot reaction, oligonucleotides are then swapped with their corresponding self-encoded removal fragments in bulk using a single Golden Gate reaction. To aid in downstream phenotyping, the library is then fused with unique DNA barcodes using the Bxb1 recombinase. We demonstrate this approach and its optimizations, to show that it is both easy to perform and efficient. This method offers simple and expedient means to create comprehensive mutagenesis libraries. ARTICLE SUMMARYResearchers in the field of molecular genetics frequently investigate protein function via mutations. Here, we present a rapid deep-mutational scanning methodology called Tiled-Region Exchange Mutagenesis that can comprehensively create mutant libraries. The approach is a multiplexed version of the established EMPIRIC mutagenesis approach and retains its simplicity. We show optimizations of the in vitro reactions to reduce cost and improve robustness. This method will be useful to researchers seeking to perform deep-mutational scanning on any gene of interest.

molecular biology↗

bioRxiv2025

Listen, who is it? A novel method for studying the nightly and annual phenologies of cave bat communities in data deficient areas of the world.

ContextBats are the only mammals who have conquered the skies and the leading mammals in terms of total biomass with the exception of humans and domestic mammals. However, the ecology of many bat species is still unknown, especially in poorly sampled regions such as Central Africa. AimsWe present the first application of an acoustic method for studying the nocturnal activity patterns and annual phenology of bat activity of cave bat communities in regions where no bat acoustic classifier exists. MethodsIn two caves (Mont Belo and Boundou) in the Republic of Congo, which are home to several species of insectivorous bats throughout the year, we set up a passive acoustic monitoring (PAM) over a period of 19 months. To identify the massive recordings collected, we used a sonotype classifier. To assign a species name or species group to the different sonotypes identified by the classifier, we collected local reference calls by capturing bats at the cave entrances. This enabled us to identify two bat groups and three species despite the absence of local call libraries. The capture sessions also allowed us to collect information about the reproductive condition of the individuals, which we interpreted in relation to the annual phenology of bat activity. To quantify bat activity, we defined the activity of each acoustic group as the number of bat passes, where a bat pass corresponds to the detection of one or several echolocation calls within a five-second interval. This standardized measure allowed us to quantify nightly and seasonal variations in activity. Key resultsThe nightly activity displayed strong peaks in the evening and the morning, except during the long rainy season, when a tri- or quadri-modal activity was detected. This more evenly distributed activity throughout the night is related to the period of juvenile rearing (gestation, parturition and lactation). For all acoustic groups, we also observed a higher activity during the rainy seasons and the short dry season, compared to the long dry season. This high activity is linked to the lactation period, the independence of young bats and potentially the mating period. Finally, the reproductive activity of insectivorous bat species is synchronized with the period of high resource availability. ConclusionThis study represents the first long-term acoustic monitoring of cave bats in the Republic of Congo. This was allowed by the use of a classifier built without any pre-existing regional call data, highlighting a practical pathway for studying bat activity in other data-deficient regions. ImplicationsInformation about the biological status of individuals captured at the monitored caves in association with the cave annual activity phenology produced with this method are key to progress in the understanding of the ecology and the conservation issues of cave bat communities, which are particularly threatened globally.

ecology↗

bioRxiv2024

Ablation of sympathetic nerve-β3 adrenergic receptor-mediated adipose tissue lipolysis attenuates alcohol-induced liver injury in mice

BACKGROUND & AIMSBinge drinking causes fat accumulation in the liver and is a known risk factor for more severe forms of alcohol-associated liver disease (ALD). Although adipocyte-released free fatty acids (FFA) have been shown to contribute to alcohol-induced liver damage, the signaling pathways that trigger lipolytic activity in adipose tissues following acute alcohol overconsumption is largely unknown. Notably, activation of sympathetic nerve-{beta}3 adrenergic receptor (ADRB3) plays a central role in sustained adipocyte lipolysis. However, whether this pathway is involved in acute alcohol-induced lipolysis remains unclear. We aimed to explore the effect of the sympathetic nerve-ADRB3-mediated pathway on adipocyte lipolytic action and fatty liver development following acute alcohol exposure. METHODSC57BL/6J mice were administered a single binge of alcohol to model acute alcohol exposure. 6-hydroxydopamine (6-OHDA) was injected systemically or locally to ablate sympathetic nerves. Mice lacking Adrb3 selectively in fat tissues (Adrb3FKO) were generated. White adipose tissue lipolysis, fatty liver development, and liver damage were investigated. RESULTSA single alcohol binge in C57BL/6J mice led to significant increases in white adipose tissue (WAT) norepinephrine (NE) content and plasma FFA levels, accompanied by the development of alcoholic hepatic steatosis. Acute alcohol-induced adipose tissue lipolysis and ALD were significantly mitigated by 6-OHDA-mediated systemic and fat tissue specific sympathetic nerve ablation. Deletion of Adrb3 in adipocytes protected mice from acute alcohol-induced adipose tissue lipolysis, hepatic fat accumulation, and liver injury. CONCLUSIONOur data indicate that binge drinking leads to the development of fatty liver and liver damage by activating adipose tissue sympathetic nerve-ADRB3-mediated lipolysis in mice. SUMMARYBinge drinking causes hepatic steatosis and liver injury through the activation of sympathetic nerve-{beta}3 adrenergic receptor-stimulated white adipose tissue lipolysis and release of free fatty acids. O_FIG O_LINKSMALLFIG WIDTH=194 HEIGHT=200 SRC="FIGDIR/small/627372v1_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@12ec139org.highwire.dtl.DTLVardef@8fa283org.highwire.dtl.DTLVardef@1f65d50org.highwire.dtl.DTLVardef@168344c_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2024

A new spatial multi-omics approach to deeply characterize human cancer tissue using a single tissue section

In the ever-changing world of digital pathology, being able to extract a maximum amount of information from a patient tissue sample is of paramount importance for better diagnosis, disease characterization, and therapeutic strategies. Recent technologies such as multiplex immunofluorescence imaging and spatial transcriptomic now enable a deep analysis of protein and gene expression while retaining the spatial context of the tissue. Here, we describe an innovative approach combining a 34-protein Phenocycler panel and transcriptome analysis using Visium on a single head and neck squamous cell carcinoma section. While protein analysis reveals the complexity of the immune phenotypes involved in the disease, transcriptome analysis reveals the intricate cellular states of cancer cells that coexist within the patients tumor. Finally, integrating both omics modalities, we uncover unique comparison of gene and protein expression of spatially resolved cellular subspaces.

cancer biology↗

bioRxiv2023

Continent-wide genomic analysis of the African buffalo (Syncerus caffer).

The African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest quality de novo genome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided surprisingly little support for the currently described four subspecies, but indicated three main lineages, in Western/Central, Eastern and Southern Africa, respectively. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management.

genomics↗

bioRxiv2023

Unveiling a Novel Memory Center in Humans: Neurochemical Identification of the Nucleus Incertus, a Key Pontine Locus Implicated in Stress and Neuropathology

BackgroundThe nucleus incertus (NI) was originally described by Streeter in 1903, as a midline region in the floor of the fourth ventricle (4V) of the human brain with an unknown function. More than a century later, the neuroanatomy of the NI including its forebrain target regions has been described in lower vertebrates, but not in humans. Therefore, we examined the neurochemical anatomy of the human NI using several markers, including the neuropeptide, relaxin-3 (RLN3), and began to explore the distribution of the NI-related RLN3 innervation of the hippocampus. MethodsHistochemical staining of serial, coronal sections (30 {micro}m) of control human postmortem pons was conducted to reveal the presence of the NI by detection of immunoreactivity (IR) for the neuronal marker, microtubule-associated protein-2 (MAP2), two markers present in rat NI, glutamic acid dehydrogenase (GAD)-65/67 and corticotrophin releasing hormone receptor 1 (CRHR1), and RLN3, which is highly expressed in a major population of NI neurons in diverse species. RLN3 and vesicular GABA transporter 1 (vGAT1) mRNA was detected by multiplex, fluorescence in situ hybridization. Postmortem pons sections containing the NI from an Alzheimers disease (AD) case were immunostained for phosphorylated-tau (AT8 antibody), to explore potential relevance to neurodegenerative diseases. Lastly, sections of human hippocampus were stained to detect RLN3-IR and somatostatin (SST)-IR, as SST is expressed in interneurons targeted by RLN3 projections in rodents. ResultsIn the dorsal, anterior-medial region of the human pons, neurons containing RLN3- and MAP2-IR, and RLN3/vGAT1 mRNA-positive neurons were observed in an anatomical pattern consistent with that of the NI in other species. GAD65/67- and CRHR1-immunopositive neurons were also detected within this area. Furthermore, RLN3- and AT8-IR were co-localized within NI neurons of an AD subject. Lastly, RLN3-IR was detected in neurons within the CA1, CA2, CA3, and DG areas of the hippocampus, in the absence of RLN3 mRNA. In the DG, RLN3- and SST-IR were co-localized in a small population of neurons. ConclusionsAspects of the anatomy of the human NI are shared across species, including a population of RLN3-expressing neurons and a RLN3 innervation of the hippocampus. Accumulation of phosphorylated-tau in the NI suggests its possible involvement in AD pathology. Further characterization of the neurochemistry of the human NI will increase our understanding of its functional role in health and disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/556922v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@f4c439org.highwire.dtl.DTLVardef@17e85f5org.highwire.dtl.DTLVardef@18ca7faorg.highwire.dtl.DTLVardef@168246c_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract Created with BioRender.com C_FIG

neuroscience↗

bioRxiv2023

Effects of biological and environmental factors on filovirus serology in bats in Guinea

BackgroundOutbreaks of Ebola disease emerge regularly in human populations on the African continent. This highly virulent haemorrhagic fever can be caused by different orthoebolaviruses from the Filoviridae family. Several bat species are believed to carry and transmit some of these viruses to people or other animal species. However, clear evidence is still lacking. Natural circulation and zoonotic transmissions of viruses are generally complex as they often involve several host species and are influenced by biological, environmental and anthropogenic factors. A better understanding of the role of bats and other wildlife in the emergence of Ebola disease outbreaks is crucial for their prevention and early detection. MethodsIn this longitudinal study we searched for antibodies against orthoebolaviruses in fruit bats in order to explore some of the factors which might influence their natural circulation. We performed serological tests on populations of 4 bat species (Eidolon helvum, Hypsignathus monstrosus, Myonycteris angolensis and Rousettus aegyptiacus) sampled longitudinally for 18 months (2018-2020) in Guinea. The analysis of 1,427 bat samples for antibodies directed against different orthoebolavirus species allowed us to test the influence of biological and environmental variables on seropositivity by using GLMM. ResultsResults showed that the presence of antibodies against one of the orthoebolaviruses antigen is more frequent in the Eidolon helvum and Rousettus aegyptiacus species, in males, in sexually immature adults, and during the dry season. ConclusionOur results suggest that host species, sex, age, reproductive life-cycle and season may play an important role in the circulation of filoviruses. This information can be used to guide further sampling to specifically characterize the orthoebolavirus species underlying the production of these antibodies and to adjust surveillance protocols at the interface between bats, humans and other animals.

microbiology↗

bioRxiv2020

PCB126-mediated effects on adipocyte energy metabolism and adipokine secretion may result in abnormal glucose uptake in muscle cells

BackgroundExposure to coplanar polychlorinated biphenyls (PCBs) is linked to the development of insulin resistance. Previous studies suggested that PCB126 alters muscle mitochondrial function through an indirect mechanism. Since PCBs are stored in fat, we hypothesized that PCB126 alters adipokine secretion, which in turn affects muscle metabolism. ObjectivesThe objectives of this study were: 1) To study the impacts of PCB126 exposure on adipocyte cytokine/adipokine secretion; 2) To determine whether adipocyte-derived factors alter glucose metabolism and mitochondrial function in myotubes when exposed to PCB126; 3) To determine whether pre-established insulin resistance alters the metabolic responses of adipocytes exposed to PCB126 and the communication between adipocytes and myotubes. Method3T3-L1 adipocytes were exposed to PCB126 (1-100 nM) in two insulin sensitivity conditions (insulin sensitive (IS) and insulin resistant (IR) adipocytes), followed by the measurement of secreted adipokines, mitochondrial function and insulin-stimulated glucose uptake. Communication between adipocytes and myotubes was reproduced by exposing C2C12 or mouse primary myotubes to conditioned medium (CM) derived from IS or IR 3T3-L1 adipocytes exposed to PCB126. Mitochondrial function and insulin-stimulated glucose uptake were then determined in myotubes. ResultsPCB126 significantly increased adipokine (adiponectin, IL-6, MCP-1, TNF-) secretion and decreased mitochondrial function, glucose uptake and glycolysis in IR but not in IS 3T3-L1 adipocytes. Altered energy metabolism in IR 3T3-L1 adipocytes was linked to decreased phosphorylation of AMP-activated protein kinase (p-AMPK) and increased superoxide dismutase 2 levels, an enzyme involved in reactive oxygen species detoxification. Exposure of myotubes to CM from PCB126-treated IR adipocytes decreased glucose uptake, without altering glycolysis or mitochondrial function. Interestingly, p-AMPK levels were increased rather than decreased in myotubes exposed to the CM of PCB126-treated IR adipocytes. ConclusionTaken together, these data suggest that increased adipokine secretion from IR adipocytes exposed to PCB126 may explain impaired glucose uptake in myotubes.

biochemistry↗