Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin‐Stimulated Glucose Uptake

• Published in: Molecular nutrition & food research Vol. 62; no. 5
• Main Authors: Mleczko, Justyna, Ortega, Francisco J., Falcon‐Perez, Juan Manuel, Wabitsch, Martin, Fernandez‐Real, Jose Manuel, Mora, Silvia
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.03.2018; John Wiley and Sons Inc
• Subjects: adipocyte; Adipocytes; Adipocytes - physiology; AKT protein; Cascades; Cell culture; Cell Hypoxia; Cells, Cultured; Conditioning; Deoxyglucose; exosome; Extracellular signal-regulated kinase; Extracellular vesicles; Extracellular Vesicles - physiology; Female; Food & Function; Glucose; Glucose - metabolism; Glucose transport; Humans; Hypoxia; Insulin; Insulin - pharmacology; Kinases; Macrophages; Obesity; Obesity - metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Signaling; Vesicles; glucose transport; insulin; exosome; adipocyte
• ISSN: 1613-4125; 1613-4133; 1613-4133
• DOI: 10.1002/mnfr.201700917

Scope We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness. Methods and results EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin‐stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin‐stimulated 2‐deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin‐mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2‐deoxyglucose uptake in adipocytes (p = 0.0159). Conclusion EVs released by stressed adipocytes impair insulin action in neighboring adipocytes. Caloric excess leads to adipose tissue expansion, with the development of local hypoxia (low oxygen) and inflammation. Hypoxic adipocytes release extracellular vesicles that impair insulin signalling and glucose uptake, contributing to adipose tissue insulin resistance.