2nd Edition of International Obesity and Metabolism Conference 2026

Abstract

Obesity alters the molecular cargo of small extracellular vesicles (sEVs) released by adipocytes.  Since adipocytes in various adipose tissue depots exhibit distinct genetic profiles, the composition of sEVs from these depots differs under obese conditions, leading to varied effects on disease pathogenesis.

High-fat diet-induced obesity (DIO) in mice significantly alters the protein profiles of small extracellular vesicles (sEVs) derived from subcutaneous adipose tissue (SAT), more so than those from epididymal (EAT) or visceral adipose tissue (VAT).  Metabolic pathways are primarily affected by the differentially expressed proteins (DEPs) in SAT-sEVs and VAT-sEVs.  Injection of SAT-sEVs into B6/J-Rab27a-Cas9-KO mice altered their metabolism, particularly fatty acid metabolism.  Several DEPs in SAT-sEVs, including ADP-ribosylation factor and mitogen-activated protein kinase kinase kinase-3, correlate with fatty acid metabolism.  Pathway analysis further revealed that SAT-sEVs influence adipocyte lipolysis and glycerophospholipid metabolism, consistent with elevated plasma levels of fatty acids, diglycerides, monoglycerides, and altered glycerophospholipid levels observed in DIO mice.

Our findings demonstrate that subcutaneous adipose tissue-derived sEVs (SAT-sEVs) influence plasma lipid profiles in obesity, suggesting novel therapeutic targets for combating obesity and related metabolic disorders.