Key Points
- To characterize the protein cargo of extracellular vesicles released by insulin-resistant and hypertrophied adipocytes and evaluate their capacity to transmit metabolic dysfunction to healthy cells.
- Established murine adipocyte cell models of insulin resistance and lipid hypertrophy induced by palmitic or oleic acid.
- Isolated extracellular vesicles and performed qualitative and quantitative protein cargo profiling using SWATH mass spectrometry.
- Conducted functional in vitro assays to assess how pathological vesicles affect healthy adipocyte differentiation, insulin sensitivity, and macrophage inflammatory cytokine expression.
- Pathological vesicles showed distinct protein profiles, with lipid-hypertrophied vesicles enriched in ceruloplasmin, mimecan, and perilipin 1, and insulin-resistant vesicles uniquely enriched in transforming growth factor-beta-induced protein ig-h3 (TFGBI).
- Exposure to vesicles derived from insulin-resistant and hypertrophied adipocytes induced hypertrophy, differentiation, and insulin resistance in healthy adipocytes.
- Vesicles shed by atrophied lipid-laden adipocytes stimulated macrophage-mediated inflammation through increased expression of IL-6 and TNFα.
Structured PICO
PPopulationMurine adipocyte cell models (insulin resistant and lipid hypertrophied)
IInterventionExtracellular vesicles (EVs) isolated from pathological adipocytes
OOutcomeProtein cargo of EVs and functional effects on healthy adipocytes and macrophagessurrogate
Extracellular vesicles from pathological adipocytes can spread metabolic dysfunction and inflammation to healthy cells, suggesting a mechanism for disease exacerbation in obesity.