Biology subjects

Ichou, F.

Publications and source records attributed to Ichou, F..

3 recordsLinked to original sources

bioRxiv2026

Obesity-related alterations in plasma metabolomics and fecal microbiota in Down syndrome Dp(16)1Yey mice

Background/ObjectivesIndividuals with Down syndrome (DS) are at increased risk of obesity and metabolic comorbidities, yet the mechanisms underlying these conditions remain unclear. Here we investigated how DS-associated genetic condition interacts with diet and metabolic pathways in the Dp(16)1Yey mouse model of DS. MethodsUntargeted plasma metabolomics was performed in Dp(16)1Yey and control mice, subjected to either control or high-fat diet (HFD). Raw data were processed, and features were annotated. Statistical analyses were conducted in R, and pathway analysis was performed with MetaboAnalyst v5.0. Fecal microbiome was obtained using 16SrRNAseq and analyzed using phyloseq in R. ResultsDiet exerted the strongest effect on mice plasma metabolome, followed by sex and genotype. Seventy-five diet-responsive metabolites were enriched in amino acid and nucleotide metabolism. Genotype-driven changes affected 34 metabolites, notably impacting amino acid and taurine-hypotaurine metabolism. Fifty-six sex-associated metabolites highlighted disruptions in aromatic amino acid biosynthesis and pyrimidine metabolism. A significant Diet*Genotype interaction was observed for five metabolites, including a marked reduction in the microbiota-derived metabolite 3-indolepropionic acid (IPA) in Dp(16)1Yey mice on HFD. Both genotype and diet exerted pronounced effects on fecal microbiome with selective depletion of the IPA-producing Clostridia in Dp1Yey mice under HFD. ConclusionSegmental trisomy in Dp(16)1Yey mice modulates the host metabolic response to dietary fat, partly through microbiota-derived metabolites such as IPA. These findings highlight the importance of genotype, diet, and microbiome interactions in shaping metabolic disease risk in DS and point toward microbiota-targeted dietary interventions.

neuroscience↗

bioRxiv2021

Dysregulated functional and metabolic response in multiple sclerosis patient macrophages correlate with a more inflammatory state, reminiscent of trained immunity

In multiple sclerosis (MS), immune cells invade the central nervous system and destroy myelin. Macrophages contribute to demyelination and myelin repair, and their role in each process depends on their ability to acquire specific phenotypes in response to external signals. Here, we assess whether defects in MS patient macrophage responses may lead to increased inflammation or lack of neuro-regenerative effects. To test this hypothesis, CD14+CD16- monocytes from MS patients and healthy controls were activated in vitro to obtain homeostatic-like, pro-inflammatory and pro-regenerative macrophages. Myelin phagocytic capacity and surface molecule expression of CD14, CD16 and HLA-DR were evaluated with flow cytometry. In parallel, macrophages were assessed through RNA sequencing and metabolomics. We observed that MS patient monocytes ex vivo recapitulate their preferential activation toward a CD16+ phenotype, a subset of pro-inflammatory cells present in MS lesions. Even in the absence of pro-inflammatory stimuli, MS patient macrophages exhibit a pro-inflammatory transcriptomic profile with higher levels of cytokine/chemokine suggesting increased recruitment capacities. Interestingly, MS patient macrophages exhibit a specific metabolic signature with a mitochondrial energy metabolism blockage resulting in a shift from oxidative phosphorylation to glycolysis. Furthermore, we observe a failure to up-regulate apoptosis effector genes in the pro inflammatory state suggesting a longer-lived pro-inflammatory macrophage population. Our results highlight an intrinsic defect of MS patient macrophages that provide evidence of innate immune cell memory in MS.

neuroscience↗

bioRxiv2020

HIGH FAT DIET STIMULATES BETA-OXIDATION, ALTERS ELECTRICAL PROPERTIES AND INDUCES ADIPOGENICITY OF ATRIA IN OBESE MICE

Metabolic disorders such as obesity are risk factors of atrial fibrillation, not only by sharing comorbidities but likely through their direct impact on atria, notably its adipogenicity. Here, we submitted mice that lack cardiac adipose tissue to a high fat diet and first studied the atrial metabolomic and lipidomic phenotypes using liquid chromatography-mass spectrometry. We found an increased consumption of free fatty acid by the beta-oxidation and an accumulation of long-chain lipids in atria of obese mice. Free fatty acid was the main substrate of mitochondrial respiration studied in the saponin-permeabilized atrial muscle. Conducted action potential recorded in atrial trabeculae was short, and ATP-sensitive potassium current was increased in perforated patch-clamp atrial myocytes of obese mice. There was histological and phenotypical evidence for an accumulation of adipose tissue in obese mice atria. Thus, an obesogenic diet transforms the energy metabolism, causes fat accumulation and induces electrical remodeling of atria myocardium. HIGHLIGHTS- Untargeted metabolomic and lipidomic analysis revealed that a high fat diet induces profound transformation of atrial energy metabolism with beta-oxidation activation and long-chain lipid accumulation. - Mitochondria respiration studied in atrial myocardial trabecula preferentially used Palmitoyl-CoA as energy substrate in obese mice. - Atria of obese mice become vulnerable to atrial fibrillation and show short action potential due to the activation of K-ATP dependent potassium current. - Adipocytes and fat molecular markers were detected in atria of obese mice together with an inflammatory profile consistence with a myocardial accumulation of fat.

physiology↗