Cécile Canlet

• French National Institute for Agriculture, Food, and Environment (INRAE)

Background: Frailty is a common geriatric syndrome characterized by increased vulnerability to stressors, reduced physiological reserves and heightened vulnerability and. It is also associated with adverse health outcomes. Given its complex phenotypes and underlying pathophysiology, there is a pressing need for robust, multidimensional biomarkers o...

Insulin and other growth factors are key regulators of liver gene expression, including in metabolic diseases. Most of the phosphoinositide 3-kinase (PI3K) activity induced by insulin is considered to be dependent on PI3Kα. We used mice lacking p110α, the catalytic subunit of PI3Kα, to investigate its role in the regulation of liver gene expression...

Capturing produced, consumed, or exchanged metabolites (metabolomics) and the result of gene expression (transcriptomics) require the extraction of metabolites and RNA. Multi-omics approaches and, notably, the combination of metabolomics and transcriptomic analyses are required for understanding the functional changes and adaptation of microorganis...

Various spectrometric methods can be used to conduct metabolomics studies. Nuclear magnetic resonance (NMR) or mass spectrometry (MS) coupled with separation methods, such as liquid or gas chromatography (LC and GC, respectively), are the most commonly used techniques. Once the raw data have been obtained, the real challenge lies in the bioinformat...

Alzheimer’s disease is strongly linked to metabolic abnormalities. We aimed to distinguish amyloid-positive people who progressed to cognitive decline from those who remained cognitively intact. We performed untargeted metabolomics of blood samples from amyloid-positive individuals, before any sign of cognitive decline, to distinguish individuals w...

Insulin and other growth factors are key regulators of liver gene expression, including in metabolic diseases. Most of the phosphoinositide 3-kinase (PI3K) activity induced by insulin is dependent on PI3Kα. We used mice lacking p110α, the catalytic subunit of PI3Kα, to investigate its role in the regulation of liver gene expression. The absence of...

Background & Aims The constitutive androstane receptor (CAR) is a nuclear receptor that binds diverse xenobiotics and whose activation leads to the modulation of the expression of target genes involved in xenobiotic detoxification and energy metabolism. Although CAR hepatic activity is considered to be higher in women than in men, its sex-dependent...

Metabolomics is now a mature phenotyping tool that provides substantial results within various scientific communities. Its application at large-scale, i.e. on large populations and/or samples, has shown its power for research activities from plant science to human epidemiology and medicine, but it still needs key methodological developments for its...

Introduction Absolute quantification of individual metabolites in complex biological samples is crucial in targeted metabolomic profiling. Objectives An inter-laboratory test was performed to evaluate the impact of the NMR software, peak-area determination method (integration vs. deconvolution) and operator on quantification trueness and precision...

Full-text available at https://hal.inrae.fr/LBE/hal-03856941v1

Obesity, which is a worldwide public health issue, is associated with chronic inflammation that contribute to long-term complications, including insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease. We hypothesized that obesity may also influence the sensitivity to food contaminants, such as fumonisin B1 (FB1), a mycotoxin prod...

Background and Aims: The constitutive androstane receptor (CAR) is a nuclear receptor able to recognize a large panel of xenobiotics leading to the modulation of the expression of its target genes involved in xenobiotic detoxication and energy metabolism. While CAR hepatic activity is thought to be higher in women than in men, its response to an ac...

Infections by multidrug-resistant Enterobacteriaceae (MRE) are life-threatening to patients. The intestinal microbiome protects against MRE colonization, but antibiotics cause collateral damage to commensals and open the way to colonization and subsequent infection. Despite the significance of this problem, the specific commensals and mechanisms th...

Glyphosate-based herbicides (GBHs) are massively used in agriculture. However, few studies have investigated the effects of glyphosate-based herbicides on avian species although they are largely exposed via their food. Here, we investigated the potential reversibility of the effects of chronic dietary exposure to glyphosate-based herbicides in broi...

For the professionals of "foie gras" production, the main quality criteria of this product are the liver weight and the technological yield after cooking (TYC). Contrary to the liver weight that is easily known after the duck evisceration, the TYC is only known after cooking the livers by pasteurization or sterilization. However, the TYC depends on...

Background and aim Obesity is a major public health issue worldwide which can leads to chronic and systemic inflammation ultimately resulting to insulin resistance and type 2 diabetes. This chronic inflammatory state contributes to long-term complications, including non-alcoholic fatty liver disease. We hypothesized here that obesity may also enhan...

Understanding the evolution of fatty liver metabolism of ducks is a recurrent issue for researchers and industry. Indeed, the increase in weight during the overfeeding period leads to an important change in the liver metabolism. However, liver weight is highly variable at the end of overfeeding within a batch of animals reared, force-fed and slaugh...

IntroductionAccuracy of feature annotation and metabolite identification in biological samples is a key element in metabolomics research. However, the annotation process is often hampered by the lack of spectral reference data in experimental conditions, as well as logistical difficulties in the spectral data management and exchange of annotations...

Fetal brain development depends on maternofetal thyroid function. In rodents and sheep, perinatal BPA exposure is associated with maternal and/or fetal thyroid disruption and alterations in central nervous system development as demonstrated by metabolic modulations in the encephala of mice. We hypothesized that a gestational exposure to a low dose...

Background In mammals, the establishment around weaning of a symbiotic relationship between the gut microbiota and its host determines long-term health. Objective The aim of this study was to identify the factors driving the co-maturation of the gut microbiota and intestinal epithelium at the suckling-to-weaning transition. We hypothesized that de...

Background Endocrine disrupting chemicals (EDCs) contribute to the etiology of metabolic disorders such as obesity, insulin resistance and hepatic dysfunction. Concern is growing about the consequences of perinatal EDC exposure on disease predisposition later in life. Metabolomics are promising approaches for studying long-term consequences of earl...

As a result of the cosmetics testing ban, safety evaluations of cosmetics ingredients must now be conducted using animal-free methods. A common approach is read across, which is mainly based on structural similarities but can also be conducted using biological endpoints. Here, metabolomics was used to assess biological effects to enable a read acro...

Tunas are among the most traded and valued fish species, and good traceability of tuna products in the world market is needed to protect both consumers and tuna stocks. To that purpose, high-resolution proton nuclear magnetic resonance (¹H NMR) spectroscopy combined with multivariate data analysis was used to investigate the molecular components of...

Metabolome profiling in biological fluids is an interesting approach for exploring markers of methane emissions in ruminants. In this study, a multiplatform metabolomics approach was used for investigating changes in milk metabolic profiles related to methanogenesis in dairy cows. For this purpose, 25 primiparous Holstein cows at similar lactation...

Understanding the evolution of fatty liver metabolism of ducks is a recurrent issue for researchers and industry. Indeed, the increase in weight during the overfeeding period leads to an important change in the liver metabolism. However, liver weight is highly variable at the end of overfeeding within a batch of animals reared, force-fed and slaugh...

The widespread failure of anthelmintic drugs against nematodes of veterinary interest requires novel control strategies. Selective treatment of the most susceptible individuals could reduce drug selection pressure but requires appropriate biomarkers of the intrinsic susceptibility potential. To date, this has been missing in livestock species. Here...

Foie gras is a traditional dish in France that contains 50 to 60% of lipids. The high-fat content of the liver improves the organoleptic qualities of foie gras and reduces its technological yield at cooking (TY). As the valorization of the liver as foie gras products is strongly influenced by the TY, classifying the foie gras in their potential tec...

Background Metabolic syndrome (MetS), a cluster of factors associated with risks of developing cardiovascular diseases, is a public health concern because of its growing prevalence. Considering the combination of concomitant components, their development and severity, MetS phenotypes are largely heterogeneous, inducing disparity in diagnosis. Meth...

Introduction Serum phenotyping of elite cyclists regarding cortisol, IGF1 and testosterone is a way to detect endocrine disruptions possibly explained by exercise overload, non-balanced diet or by doping. This latter disruption-driven approach is supported by fundamental physiology although without any evidence of any metabolic markers. Objectives...

The effects of low doses of toxicants are often subtle and information extracted from metabolomic data alone may not always be sufficient. As end products of enzymatic reactions, metabolites represent the final phenotypic expression of an organism and can also reflect gene expression changes caused by this exposure. Therefore, the integration of me...

The widespread failure of anthelmintic drugs against nematodes of veterinary interest requires novel control strategies. Selective treatment of the most susceptible individuals could reduce drug selection pressure but requires appropriate biomarkers of the intrinsic susceptibility potential. To date, this has been missing in livestock species. Here...

Introduction et but de l’étude Le glyphosate est l’herbicide le plus vendu en France. Son usage intensif est associé à l’exposition chronique de l’homme via l’eau et l’alimentation. La molécule agit en inhibant l’EPSPS, une enzyme indispensable aux plantes mais aussi à de nombreuses bactéries pour la synthèse d’acides aminés. Cette enzyme est retro...

The foie gras is an emblematic product of French gastronomy composed of waterfowl fatty liver. The organoleptic qualities of this product depend on the liver characteristics such as liver weight (LW) and technological yield (TY) at cooking. One of the main issues for producers is to classify the foie gras with high or low technological quality befo...

Metabolomics is a promising approach to characterize phenotypes or to identify biomarkers. It is also easily accessible through NMR, which can provide a comprehensive understanding of the metabolome of any living organisms. However, the analysis of 1H NMR spectrum remains difficult, mainly due to the different problems encountered to perform automa...

The gut microbiota plays a key role in intestinal development at the suckling-to-weaning transition. The objective of this study was to analyze the production of metabolites by the gut microbiota in suckling and weaned piglets. We studied piglets raised in two separate maternity farms and weaned at postnatal day 21 in the same farm. The fecal metab...

In mammalian species, the first days after birth are an important period for survival and the mortality rate is high before weaning. In pigs, perinatal deaths average 20% of the litter, with important economic and societal consequences. Maturity is one of the most important factors that influence piglet survival at birth. Maturity can be defined as...

Background We recently demonstrated that chronic dietary exposure to a mixture of pesticides at low-doses induced sexually dimorphic obesogenic and diabetogenic effects in adult mice. Perinatal pesticide exposure may also be a factor in metabolic disease etiology. However, the long-term consequences of perinatal pesticide exposure remain controvers...

Metabolic disorders induced by endocrine disruptors (ED) may contribute to amphibian population declines but no transgenerational studies have evaluated this hypothesis. Here we show that Xenopus tropicalis, exposed from the tadpole stage, to the ED benzo[a]pyrene (BaP, 50 ng.L⁻¹) produced F2 progeny with delayed metamorphosis and sexual maturity....

Metabolomics is a promising approach to characterize phenotypes or to identify biomarkers. It is also easily accessible through NMR, which can provide a comprehensive understanding of the metabolome of any living organisms. However, the analysis of ¹ H NMR spectrum remains difficult, mainly due to the different problems encountered to perform autom...

There is scarce information on whether inhibition of rumen methanogenesis induces metabolic changes on the host ruminant. Understanding these possible changes is important for the acceptance of methane-reducing practices by producers. In this study we explored the changes in plasma profiles associated with the reduction of methane emissions. Plasma...

The postprandial period represents one of the most challenging phenomena in whole-body metabolism, and it can be used as a unique window to evaluate the phenotypic flexibility of an individual in response to a given meal, which can be done by measuring the resilience of the metabolome. However, this exploration of the metabolism has never been appl...

In suckling mammals, the onset of solid food ingestion is coincident with the maturation of the gut barrier. This ontogenic process is driven by the colonization of the intestine by the microbiota. However, the mechanisms underlying the microbial regulation of the intestinal development in early life are not fully understood. Here, we studied the c...

Peroxisome proliferator activated receptor α (PPARα) acts as a fatty acid sensor to orchestrate the transcription of genes coding for rate-limiting enzymes required for lipid oxidation in hepatocytes. Mice only lacking Pparα in hepatocytes spontaneously develop steatosis without obesity in aging. Steatosis can develop into non alcoholic steatohepat...

The objective of this study was to analyze in piglets the impact of weaning on the production of metabolites by gut bacteria and to determine whether early life environment influences the functional maturation of the gut microbiota. Fecal metabolome and microbiome were analyzed in piglets raised in two separate maternity farms and mixed at weaning....

In mammalian species, the first days after birth are an important period for survival and the rates of mortality before weaning are high. In pigs, the perinatal deaths average 20% of the litter, with important economic and societal consequences. Among the factors influencing piglet survival at birth, the maturity is likely to be one of the most imp...

Metabolomics has found numerous applications in the study of liver metabolism in health and disease. Metabolomics studies can be conducted in a variety of biological matrices ranging from easily accessible biofluids such as urine, blood or feces, to organs, tissues or even cells. Sample collection and storage are critical steps for which standard o...

IntroductionThe salivary metabolome has been increasingly studied over the past ten years due to the potential of saliva as a non-invasive source of biomarkers. However, although saliva has been studied in relation to various diseases, its dynamic evolution during life is not known. This is particularly true for the first months of life. Infancy is...

Low-level contamination of food and feed by deoxynivalenol (DON) is unavoidable. We investigated the effects of subclinical treatment with DON, and supplementation with probiotic yeast Saccharomyces cerevisiae boulardii I1079 as a preventive strategy in piglets. Thirty-six animals were randomly assigned to either a control diet, a diet contaminated...

Hepatic metabolites provide valuable information on the physiological state of an organism, and thus, they are monitored in many clinical situations. Typically, monitoring requires several analyses for each class of targeted metabolite, which is time consuming. The present study aimed to evaluate a proton nuclear magnetic resonance (¹H-NMR) method...

Motivation: In metabolomics, the detection of new biomarkers from Nuclear Magnetic Resonance (NMR) spectra is a promising approach. However, this analysis remains difficult due to the lack of a whole workflow that handles spectra pre-processing, automatic identification and quantification of metabolites and statistical analyses, in a reproducible...

Blood circulation mainly aims at distributing the nutrients required for tissue metabolism and collecting safely the by-products of all tissues to be further metabolized or eliminated. The simultaneous study of arterial (A) and venous (V) specific metabolites therefore has appeared to be a more relevant approach to understand and study the metaboli...

Background The World Health Organization classified processed and red meat consumption as “carcinogenic” and “probably carcinogenic”, respectively, to humans. Haem iron from meat plays a role in the promotion of colorectal cancer in rodent models, in association with enhanced luminal lipoperoxidation and subsequent formation of aldehydes. Here, we...

Lipids are key molecules in various biological processes, thus their quantification is a crucial point in a lot of studies and should be taken into account in lipidomics development. This family is complex and presents a very large diversity of structures, so analyzing and quantifying all this diversity is a real challenge. In this review, the diff...

Objectives: Peroxisome proliferator activated receptor α (PPARα) acts as a fatty acid sensor to orchestrate the transcription of genes coding for rate-limiting enzymes required for lipid oxidation in hepatocytes. Mice only lacking Pparα in hepatocytes spontaneously develop steatosis without obesity in aging. Altough steatosis is a benign condition...

Being able to explore the metabolism of broad metabolizing cells is of critical importance in many research fields. This article presents an original modelling solution combining metabolic network and omics data to identify modulated metabolic pathways and changes in metabolic functions occurring during differentiation of a human hepatic cell line...

Introduction et but de l’étude L’alimentation du nouveau-né joue un rôle déterminant dans la mise en place du microbiote intestinal et de ses interactions avec l’hôte, conditionnant la santé du futur adulte. Nous avons précédemment montré que l’incorporation de matière grasse laitière (MGL) associée ou non au probiotique Lactobacillus fermentum CEC...

The quality of milk metabolome analyzed by nuclear magnetic resonance (NMR) is greatly influenced by the way samples are prepared. Although this analytical method is increasingly used to study milk metabolites, a thorough examination of available sample preparation protocols for milk has not been reported yet. We evaluated the performance of eight...

The model xeno-estrogen bisphenol A (BPA) has been extensively studied over the past two decades, contributing to major advances in the field of endocrine disrupting chemicals research. Besides its well documented adverse effects on reproduction and development observed in rodents, latest studies strongly suggest that BPA disrupts several endogenou...

In metabolomics, the detection of new biomarkers from NMR spectra is a promising approach. However, this analysis remains difficult due to the lack of a whole workflow that handles spectra pre-processing, automatic identification and quantification of metabolites and statistical analyses. We present ASICS , an R package that contains a complete wor...

Clinical and animal studies have demonstrated beneficial effects of early consumption of dairy lipids and a probiotic, Lactobacillus fermentum (Lf), on infant gut physiology. The objective of this study was to investigate their long-term effects on gut microbiota and host entero-insular axis and metabolism. Piglets were suckled with a milk formula...

The use of pesticides exposes humans to numerous harmful molecules. Exposure in early-life may be responsible for adverse effects in later life. This study aimed to assess the metabolic modifications induced in pregnant rats and their offspring by a pesticide mixture representative of human exposure. Ten pregnant rats were exposed to a mixture of e...

Bucket Table corresponding to NMR spectra from aqueous liver extract of male offspring collected at GD21. (XLSX)

Bucket Table corresponding to NMR spectra from urine of dams collected at GD15. (XLSX)

Bucket Table corresponding to NMR spectra from aqueous liver extract of female offspring collected at GD21. (XLSX)

Bucket Table corresponding to NMR spectra from plasma of male offspring collected at GD21. (XLSX)

Bucket Table corresponding to NMR spectra from aqueous brain extract of female offspring collected at GD21. (XLSX)

Bucket Table corresponding to NMR spectra from plasma of dams collected at GD21. (XLSX)

Bucket Table corresponding to NMR spectra from aqueous liver extracts of dams collected at GD21. (XLSX)

Bucket Table corresponding to NMR spectra from aqueous brain extracts of dams collected at GD21. (XLSX)

Bucket Table corresponding to NMR spectra from aqueous brain extract of male offspring collected at GD21. (XLSX)

Background: Epidemiological evidence suggests a link between pesticide exposure and the development of metabolic diseases. However, most experimental studies have evaluated the metabolic effects of pesticides using individual molecules, often at nonrelevant doses or in combination with other risk factors such as high-fat diets. Objectives: We ai...

Aflatoxins are found as food contaminant and some of them demonstrate a carcinogenic effect. The aflatoxins biosynthetic pathway involves 15 successive steps. The aim of this study was to compare the toxicity of aflatoxins and their precursors in three human cell lines. We tested the four aflatoxins and two of their metabolites; three early metabol...