Camu-Camu Reduces Obesity and Improves Diabetic Profiles of Obese and Diabetic Mice : A Dose-Ranging Study

Overweight, obesity, and their comorbidities are currently considered a major public health concern. Today considerable efforts are still needed to develop efficient strategies able to attenuate the burden of these diseases. Nutritional interventions, some with plant extracts, present promising health benefits. In this study, we evaluated the action of Camu-Camu (Myrciaria dubia), an Amazonian fruit rich in polyphenols and vitamin C, on the prevention of obesity and associated disorders in mice and the abundance of Akkermansia muciniphila in both cecum and feces. Methods: We investigated the dose-response effects of Camu-Camu extract (CCE) in the context of high-fat-diet (HFD)-induced obesity. After 5 weeks of supplementation, we demonstrated that the two doses of CCE differently improved glucose and lipid homeostasis. The lowest CCE dose (62.5 mg/kg) preferentially decreased non-HDL cholesterol and free fatty acids (FFA) and increased the abundance of A. muciniphila without affecting liver metabolism, while only the highest dose of CCE (200 mg/kg) prevented excessive body weight gain, fat mass gain, and hepatic steatosis. Both doses decreased fasting hyperglycemia induced by HFD. In conclusion, the use of plant extracts, and particularly CCE, may represent an additional option in the support of weight management strategies and glucose homeostasis alteration by mechanisms likely independent from the modulation of A. muciniphila abundance.Peer reviewe

Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: Application to acetaminophen injury

International audienceWe have analyzed transcriptomic, proteomic and metabolomic profiles of hepatoma cells cultivated inside a microfluidic biochip with or without acetaminophen (APAP). Without APAP, the results show an adaptive cellular response to the microfluidic environment, leading to the induction of anti-oxidative stress and cytoprotective pathways. In presence of APAP, calcium homeostasis perturbation, lipid peroxidation and cell death are observed. These effects can be attributed to APAP metabolism into its highly reactive metabolite. N-acetyl-p-benzoquinone imine (NAPQI). That toxicity pathway was confirmed by the detection of GSH-APAP, the large production of 2-hydroxybutyrate and 3-hydroxybutyrate, and methionine, cystine, and histidine consumption in the treated biochips. Those metabolites have been reported as specific biomarkers of hepatotoxicity and glutathione depletion in the literature. In addition, the integration of the metabolomic, transcriptomic and proteomic collected profiles allowed a more complete reconstruction of the APAP injury pathways. To our knowledge, this work is the first example of a global integration of microfluidic biochip data in toxicity assessment. Our results demonstrate the potential of that new approach to predictive toxicology

Protéagineux : des ressources génétiques à l’innovation variétale

National audiencePeaMUST brings together 26 partners from the public and private sectors, having a large range of competencies, from geneticists to biochemists, stakeholders to farmers. PeaMUST is tailored to provide new insights into the mechanisms of multi-stress resistance and enable efficient and rapid exploitation of useful genetic diversity – natural and induced – to develop improved crop varieties with a more stable yield. The overall objective is to develop novel pea varieties and optimize plant-symbiotic interactions for stabilized seed yield and quality, in the context of climate change and pesticide reduction

ETUDE DE LA RESISTANCEAU CHLORAMPHENICOL DANS UNE POPULATION DE SALMONELLES BOVINES

MARCY L'ETOILE-Ec.Nat.Vétéri (691272301) / SudocSudocFranceF

Exploiting Glomus intraradices sequencing data to dissect molecular mechanisms of plant genome control over fungal gene expression in mycorrhiza

International audienc

Preliminary data on the disposition of Benzo[c]fluorene in rat

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants and food contaminants. Part of them is mutagenic/genotoxic in vitro and in vivo and has shown clear carcinogenic effects in mammals. Therefore, these chemicals are of public health concern and require appropriate hazard characterization. The genotoxic process resulting in the carcinogenicity of PAHs is due to the formation of highly reactive metabolites, produced through different metabolic pathways. Among the PAH found in food samples, benzo[c]fluorene (B[c]F) was demonstrated to be carcinogenic in rodents 1,2 and the occurrence of corresponding pulmonary adducts has been demonstrated3. JECFA4 and EFSA5 recently highlighted the need for additional occurrence and toxicological data regarding this compound. In this context, we started to study B[c]F distribution and biotransformation in Sprague Dawley rats exposed to a single oral dose of radiolabelled B[c]F (20 µg/kg body weight). Extraction protocols of B[c]F residues from rats tissues, fluids, and excreta were developed with the aim to analyze both parental B[c]F and metabolites. Metabolic profiles were determined by radio-HPLC. Analysis of 0-24h urine samples showed an extensive renal excretion and the presence of many metabolites (>20). Liquid-solid extractions from liver samples excised 24h post-dose resulted in more than 50% unextractable radioactivity suggesting the presence of bound residues. Radio-HPLC profiles of extracts indicated the presence of approximately 30% of unmetabolized B[c]F, as well as several polar metabolites. Experimental developments and analyses of additional tissues and fluids are in progress, with the aim to better understand the metabolic mechanisms that trigger the carcinogenicity of this molecule. Our data will be used to develop a PBPK model in order to describe the toxicokinetics of B[c]F in rats and ultimately to extrapolate the toxicokinetics to humans

Pasteurized Akkermansia muciniphila improves glucose metabolism is linked with increased hypothalamic nitric oxide release

Background and objective: Pasteurized Akkermansia muciniphila cells have shown anti-diabetic effects in rodents and human. Although, its primary site of action consists in maintaining the gut barrier function, there are no study exploring if A. muciniphila controls glycemia via a gut to brain axis. Targeting the gut motility represents an alternative pathway to treat hyperglycemia. Here, we tested the impact of pasteurized A. muciniphila on gut motility, gut-brain axis and glucose metabolism.Methods: We used mice fed a 45% high-fat (HFD) treated or not with pasteurized A. muciniphila MucT during 12 weeks. We measured the effects of the treatment on body weight gain, glucose metabolism (insulin, glycemia, glucose tolerance), gut contraction and enteric neurotransmitter release, and hypothalamic nitric oxide (NO) release.Results: We show that pasteurized A. muciniphila exerts positive effects on different metabolic parameters such as body weight, fat mass, insulin, glycemia and glucose tolerance. This could be explained by the ability of pasteurized A. muciniphila supplementation to decrease duodenal contraction and to increase hypothalamic NO release in HFD mice.Conclusion: We demonstrate a novel mode of action of pasteurized A. muciniphila explaining its beneficial impact on the control of glycemia in a preclinical model of type 2 diabetes via gut-brain axis signaling.Peer reviewe

liver-kidney microfluidic bioreactor for cell co-culture in drug studies

International audienc