Biology subjects

Ayciriex, S.

Publications and source records attributed to Ayciriex, S..

6 recordsLinked to original sources

bioRxiv2025

N-acetyl-phenylalanine induces hepatic steatosis in MASLD by disrupting ER-mitochondria calcium coupling and mitochondrial lipid oxidation

Background & AimsThe gut-liver axis and hepatic ER-mitochondria miscommunication (at contact sites called MAMs) are involved in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the role of circulating aromatic amino acids (AAA) derived from phenylalanine and tyrosine in MASLD potentially through MAM alterations. MethodsWe analyzed AAA metabolomic profiles in individuals with and without MASLD and validated findings in a biopsy-proven cohort. The pro-steatogenic effect of MASLD-associated AAAs was validated in vitro using lipid labeling, MAM structural/functional assays, and palmitate-induced respiration. In vivo effects were tested in mice fed with candidate AAAs, and MAM involvement was confirmed by expressing a specific organelle linker in vitro and in vivo. ResultsN-acetyl-phenylalanine (NAPA) was strongly associated with hepatic steatosis and correlated with specific gut microbes. In vitro, NAPA promoted lipid accumulation by impairing ER-mitochondria calcium exchange via a LAT1-dependent electrogenic mechanism, reducing mitochondrial lipid oxidation. Chronic NAPA administration in mice induced steatosis and MAM disruption. Notably, enhancing ER-mitochondria contacts with an organelle linker prevented NAPA-induced steatosis in vitro and in vivo. Additionally, other phenylalanine- and tyrosine-derived AAAs reproduced NAPAs effects, suggesting a class-dependent mechanism. ConclusionNAPA emerges as a MASLD-promoting metabolite, contributing to hepatic steatosis by disrupting ER-mitochondria calcium coupling and mitochondrial lipid oxidation. Lay SummaryThe gut-liver axis is a key component of the development of MASLD, and circulating gut-derived metabolites, notably AAAs derived from phenylalanine and tyrosine metabolism, have been associated with MASLD. However, the specific causal mechanisms of these AAA metabolites in MASLD development remain unexplored. Here, we identified NAPA, a gut microbiome linked metabolite elevated in MASLD patients, as a causal driver of hepatic steatosis both in vitro and in vivo. Mechanistically, NAPA alters ER-mitochondria calcium coupling leading to reduced mitochondrial lipid oxidation, highlighting a new mechanism with potential therapeutic implications. HIGHLIGHTS- Circulating NAPA levels are increased in MASLD patients and correlate with hepatic steatosis. - NAPA levels result from a complex host-microbiota interplay - NAPA induces lipid accumulation by dampening ER-mitochondria calcium coupling and mitochondrial lipid oxidation. - NAPA disrupts MAMs by a LAT1-mediated electrogenic mechanism. - Other Phe- and Tyr-mediated metabolites have the same pro-steatogenic effect than NAPA pointing to a class-dependent effect.

pathology↗

bioRxiv2024

Proteogenomic reconstruction of organ-specific metabolic networks in an environmental sentinel species, the amphipod Gammarus fossarum

Metabolic pathways are targets of environmental contaminants underlying a large variability of toxic effects throughout biodiversity. However, the systematic reconstruction of metabolic pathways remains limited in environmental sentinel species due to the lack of available genomic data in many taxa of animal diversity. In order to improve the knowledge of the metabolism of sentinel species, in this study we used a multi-omics approach to reconstruct the most comprehensive map of metabolic pathways for a crustacean model in biomonitoring, the amphipod Gammarus fossarum. We revisited the assembly of RNA-seq data by de novo approaches drastically reducing RNA contaminants and transcript redundancy. We also acquired extensive mass spectrometry shotgun proteomic data on several organs from G. fossarum males and females to identify organ-specific metabolic profiles. The G. fossarum metabolic pathway reconstruction (available through the metabolic database GamfoCyc) was performed by adapting the genomic tool CycADS and we identified 377 pathways representing 7,630 annotated enzymes, 2,610 enzymatic reactions and the expression of 858 enzymes was experimentally validated by proteomics. Our analysis shows organ-specific metabolic profiles, such as an elevated abundance in enzymes involved in ATP biosynthesis and fatty acid beta-oxidation indicative of the high-energy requirement of the gills, or the key anabolic and detoxification role of the hepatopancreatic caeca, as exemplified by the specific expression of the retinoid biosynthetic pathways and glutathione synthesis. In conclusion, the multi-omics data integration performed in this study provides new resources to investigate metabolic processes in crustacean amphipods and their role in mediating the effects of environmental contaminant exposures in sentinel species.

molecular biology↗

bioRxiv2023

Concomitant investigation of crustacean amphipods lipidome and metabolome during molting stage by Zeno SWATH Data-Independent Acquisition coupled with Electron Activated Dissociation and machine learning

BackgroundDIA (Data-Independent Acquisition) is a powerful technique in Liquid Chromatography coupled with high-resolution tandem Mass Spectrometry (LC-MS/MS) in metabolomics and lipidomics, for comprehensive profiling of molecules in biological samples. It provides unbiased coverage, improved reproducibility, and quantitative accuracy compared to Data-Dependent Acquisition (DDA). Combined with the Zeno trap and Electron-Activated Dissociation (EAD), DIA enhances data quality and structural elucidation compared to conventional fragmentation under CID. These tools were applied to study the lipidome and metabolome of the freshwater amphipod Gammarus fossarum, successfully discriminating stages and highlighting significant biological features. Despite being underused, DIA, along with the Zeno trap and EAD, holds great potential for advancing research in the omics field. ResultsDIA combined with the Zeno trap enhances detection reproducibility compared to conventional DDA, improving fragmentation spectra quality and putative identifications. LC coupled with Zeno-SWATH-DIA methods were used to study molecular changes in reproductive cycle of female gammarids. Multivariate data analysis including Principal Component Analysis and Partial Least Square Discriminant Analysis successfully identified statistically significant features responsible for group segregation. EAD fragmentation helped to identify unknown features and to confirm their molecular structure using fragmentation spectra DB annotation or machine learning. EAD database matching accurately annotated five glycerophospholipids, including the position of double bonds on fatty acid chain moieties. SIRIUS database predicted structures of unknown features based on experimental fragmentation spectra to compensate for database incompleteness. SignificanceReproducible detection of features and confident identification of putative compounds are pivotal stages within analytical pipelines. The DIA approach combined with Zeno pulsing and EAD synergistically enhances detection sensitivity while providing orthogonal fragmentation information, thereby facilitating a comprehensive and insightful exploration of pertinent biological molecules associated with the reproductive cycle of gammarids. The developed methodology holds great promises for identifying biomarkers of significance in the field of environmental assessment. HighlightsO_LIAdvancements in Data-Independent-Acquisition methods for lipidomics and metabolomics. C_LIO_LIZeno pulsing improves sensitivity in fragment detection and compound identification. C_LIO_LIComprehensive structure elucidation of lipids and metabolites using EAD fragmentation. C_LI

biochemistry↗

bioRxiv2023

Lipidome unsaturation affects the morphology and proteome of the Drosophila eye.

While the proteome of an organism is largely determined by the genome, the lipidome is shaped by a poorly understood interplay of environmental factors and metabolic processes. To gain insights into the underlying mechanisms, we analyzed the impacts of dietary lipid manipulations on the ocular proteome of Drosophila melanogaster. We manipulated the lipidome with synthetic food media that differed in the supplementation of an equal amount of saturated or polyunsaturated triacylglycerols. This allowed us to generate flies whose eyes had a highly contrasting length and unsaturation of glycerophospholipids, the major lipid class of biological membranes, while the abundance of other membrane lipid classes remained unchanged. By bioinformatically comparing the resulting ocular proteomic trends and contrasting them with the impacts of vitamin A deficiency, we identified ocular proteins whose abundances are differentially affected by lipid saturation and unsaturation. For instance, we unexpectedly identified a group of proteins that have muscle-related functions and increase their abundances in the eye upon lipidome unsaturation but are unaffected by lipidome saturation. Moreover, we identified two differentially lipid-responsive proteins involved in stress responses, Turandot A and Smg5, whose abundances decrease with lipid unsaturation. Lastly, we discovered that the ocular lipid class composition is robust to dietary changes and propose that this may be a general homeostatic feature of the organization of eukaryotic tissues, while the length and unsaturation of fatty acid moieties is more variable to compensate environmental challenges. We anticipate that these insights into the molecular responses of the Drosophila eye proteome to specific lipid manipulations will guide the genetic dissection of the mechanisms that maintain visual function when the eye is exposed to dietary challenges.

neuroscience↗

bioRxiv2023

Eye proteome of Drosophila melanogaster

The Drosophila melanogaster eye is a popular model to elucidate the molecular mechanisms that underlie the structure and function of the eye as well as the causes of retinopathies. For instance, the Drosophila eye has been used to investigate the impacts of ageing and environmental stresses such as light-induced damage or dietary deficiencies. Moreover, large-scale screens have isolated genes whose mutation causes morphological and functional ocular defects, which includes key components of the phototransduction cascade. However, the proteome of the Drosophila eye is poorly characterized. Here, we used GeLC-MS/MS to quantify 3516 proteins he adult Drosophila melanogaster eye and provide a generic and expandable resource for further genetic, pharmacological, and dietary studies.

neuroscience↗

bioRxiv2020

Shotgun lipidomics and mass spectrometry imaging unveil diversity and dynamics in lipid composition in Gammarus fossarum

Sentinel species are playing an indispensable role in monitoring environmental pollution in aquatic ecosystems. Many pollutants found in water prove to be endocrine disrupting chemicals that could cause disruptions in lipid homeostasis in aquatic species. A comprehensive profiling of the lipidome of these species is thus an essential step towards understanding the mechanism of toxicity induced by pollutants. We here extensively examined both the composition and spatial distribution of lipids in freshwater crustacean Gammarus fossarum. The baseline lipidome of gammarids of different gender and reproductive stage was established by high throughput shotgun lipidomics. Spatial lipid mapping by high resolution mass spectrometry imaging led to the discovery of sulfate-based lipids in hepatopancreas and their accumulation in mature oocytes. We uncovered in G. fossarum a diverse and dynamic lipid composition that deepens our understanding of the biochemical changes during development and which could serve as a reference for future ecotoxicological studies.

biochemistry↗