Novel insight into the lipid network of plasma extracellular vesicles reveal sex-based differences in the lipidomic profile of alcohol use disorder patients
Carla Perpiñá-Clérigues, Susana Mellado, Cristina Galiana-Roselló, María Fernández-Regueras, Miguel Marcos, Francisco García-García, María Pascual
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引用次数: 0
Abstract
Alcohol use disorder (AUD) is one of the most common psychiatric disorders, with the consumption of alcohol considered a leading cause of preventable deaths worldwide. Lipids play a crucial functional role in cell membranes; however, we know little about the role of lipids in extracellular vesicles (EVs) as regulatory molecules and disease biomarkers. We employed a sensitive lipidomic strategy to characterize lipid species from the plasma EVs of AUD patients to evaluate functional roles and enzymatic activity networks to improve the knowledge of lipid metabolism after alcohol consumption. We analyzed plasma EV lipids from AUD females and males and healthy individuals to highlight lipids with differential abundance and biologically interpreted lipidomics data using LINEX2, which evaluates enzymatic dysregulation using an enrichment algorithm. Our results show, for the first time, that AUD females exhibited more significant substrate-product changes in lysophosphatidylcholine/phosphatidylcholine lipids and phospholipase/acyltransferase activity, which are potentially linked to cancer progression and neuroinflammation. Conversely, AUD males suffer from dysregulated ceramide and sphingomyelin lipids involving sphingomyelinase, sphingomyelin phosphodiesterase, and sphingomyelin synthase activity, which relates to hepatotoxicity. Notably, the analysis of plasma EVs from AUD females and males demonstrates enrichment of lipid ontology terms associated with “negative intrinsic curvature” and “positive intrinsic curvature”, respectively. Our methodological developments support an improved understanding of lipid metabolism and regulatory mechanisms, which contribute to the identification of novel lipid targets and the discovery of sex-specific clinical biomarkers in AUD. Alcohol use disorder (AUD) is one of the most common psychiatric disorders, with the consumption of alcohol considered a leading cause of preventable deaths worldwide. Lipids play a crucial functional role in cell membranes; however, we know little about the role of lipids in extracellular vesicles (EVs) as regulatory molecules and disease biomarkers. We employed a sensitive lipidomic strategy to characterize lipid species from the plasma EVs of AUD patients to evaluate functional roles and enzymatic activity networks to improve the knowledge of lipid metabolism after alcohol consumption. We analyzed plasma EV lipids from AUD females and males and healthy individuals to highlight lipids with differential abundance and biologically interpreted lipidomics data using LINEX2, which evaluates enzymatic dysregulation using an enrichment algorithm. Our results show, for the first time, that AUD females exhibited more significant substrate-product changes in lysophosphatidylcholine/phosphatidylcholine lipids and phospholipase/acyltransferase activity, which are potentially linked to cancer progression and neuroinflammation. Conversely, AUD males suffer from dysregulated ceramide and sphingomyelin lipids involving sphingomyelinase, sphingomyelin phosphodiesterase, and sphingomyelin synthase activity, which relates to hepatotoxicity. Notably, the analysis of plasma EVs from AUD females and males demonstrates enrichment of lipid ontology terms associated with “negative intrinsic curvature” and “positive intrinsic curvature”, respectively. Our methodological developments support an improved understanding of lipid metabolism and regulatory mechanisms, which contribute to the identification of novel lipid targets and the discovery of sex-specific clinical biomarkers in AUD.
期刊介绍:
Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research.
Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.