Molecular Imprints of Clinical Comorbidities in Hypothalamic Extracellular Vesicles at the Onset of Obesity.

ACS Omega

Biomedical Research Institute of Lleida Dr. Pifarré Foundation (IRBLLEIDA)+Pec Proteomics Research Group (+PPRG)Neuroscience Area, University Hospital Arnau de Vilanova (HUAV), 80 Avenue Rovira Roure, 25198 Lleida, Catalonia, Spain.

Published: June 2025


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Article Abstract

The onset of obesity is characterized by early physiological and molecular changes, including leptin resistance and hypothalamic dysfunction, preceding significant weight gain and metabolic complications. Extracellular vesicles (EVs) are key mediators of intercellular communication, reflecting early pathological shifts in metabolic disorders. This study investigates the role of hypothalamic EVs (hEVs) in early obesogenic insult and their potential implications for obesity-related comorbidities. Using a hamster model fed a high fat diet for 30 days, next-generation proteomics revealed altered hEV protein compositions linked to cellular metabolism, neuroinflammation, and metabolic dysfunction, mirroring early obesity-related dysfunction. These findings highlight the adaptive molecular profiles of hEVs during early obesogenic insult and their potential as biomarkers and molecular mediators in obesity progression and its comorbidities. In conclusion, this study provides new insights into the molecular mechanisms underlying the onset of obesity and highlights hEVs as promising targets for early detection and intervention.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163634PMC
http://dx.doi.org/10.1021/acsomega.5c02274DOI Listing

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