TY - JOUR
T1 - Circulating adipocyte-derived extracellular vesicles are novel markers of metabolic stress
AU - Eguchi, Akiko
AU - Lazic, Milos
AU - Armando, Aaron M.
AU - Phillips, Susan A.
AU - Katebian, Roia
AU - Maraka, Spyridoula
AU - Quehenberger, Oswald
AU - Sears, Dorothy D.
AU - Feldstein, Ariel E.
N1 - Funding Information:
The authors would like to thank Dr. Marilyn Farquhar (University of California, San Diego, UCSD) for the use of the electron microscopy facility; Timo Meerloo for electron microscopy sample preparation; Dr. Majid Ghassemian of the Biomolecular and Proteomics Mass Spectrometry facility (UCSD) for the proteomics study; Dr. Gary Hardiman, director of UCSD Biomedical Genomics Facility (BIOGEM); and Dr. Roman Sasik for analysis of the sequencing study. We acknowledge One World Lab for the assistance with selecting antibodies and providing test size quantities. This work was supported by NIH grant (U01 AA022489) and (DK082451) to AEF, Gilead research scholars program in liver disease to AE, and P. Robert Majumder Charitable Foundation to DDS.
Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - Abstract: We recently reported that stressed adipocytes release extracellular vesicles (EVs) that act as “find-me” signals to promote macrophage migration and activation. In this study, we performed a comprehensive characterization of stressed adipocyte-derived EVs, assessing their antigenic composition, lipidomics, and RNA profiles. Perilipin A was identified as one of the adipose-specific proteins and studied as a potential novel biomarker to detect adipocyte-derived EVs in circulation. Circulating EVs were significantly increased in mice with diet-induced obesity (DIO) and in obese humans with metabolic syndrome compared to lean controls. This increase was associated with decreased glucose tolerance in the DIO mice and metabolic dysfunction, elevated insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) in the obese humans. EVs from both DIO mice and obese humans were enriched in perilipin A, a central gatekeeper of the adipocyte lipid storehouse and a marker of adipocyte differentiation. In obese humans, circulating levels of EVs enriched in perilipin A were dynamic, decreasing 35 % (p < 0.05) after a 3-month reduced calorie diet intervention. This translational study provides an extensive characterization of adipocyte-derived EVs. The findings identify perilipin A as a novel biomarker of circulating EVs of adipocyte origin and support the development of circulating perilipin A-positive EVs as indicators of adipose tissue health. Key message: • Extensive characterization of 3T3L1 EVs identified perilipin A in their composition. • Circulating EVs are elevated in obese mice and associated with glucose intolerance. • Circulating EVs are elevated in obese human and correlated with metabolic factors. • Perilipin A and EV levels are increased in the circulation of obese mice and human. • Circulating EV and perilipin A levels decrease with low calorie intervention.
AB - Abstract: We recently reported that stressed adipocytes release extracellular vesicles (EVs) that act as “find-me” signals to promote macrophage migration and activation. In this study, we performed a comprehensive characterization of stressed adipocyte-derived EVs, assessing their antigenic composition, lipidomics, and RNA profiles. Perilipin A was identified as one of the adipose-specific proteins and studied as a potential novel biomarker to detect adipocyte-derived EVs in circulation. Circulating EVs were significantly increased in mice with diet-induced obesity (DIO) and in obese humans with metabolic syndrome compared to lean controls. This increase was associated with decreased glucose tolerance in the DIO mice and metabolic dysfunction, elevated insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) in the obese humans. EVs from both DIO mice and obese humans were enriched in perilipin A, a central gatekeeper of the adipocyte lipid storehouse and a marker of adipocyte differentiation. In obese humans, circulating levels of EVs enriched in perilipin A were dynamic, decreasing 35 % (p < 0.05) after a 3-month reduced calorie diet intervention. This translational study provides an extensive characterization of adipocyte-derived EVs. The findings identify perilipin A as a novel biomarker of circulating EVs of adipocyte origin and support the development of circulating perilipin A-positive EVs as indicators of adipose tissue health. Key message: • Extensive characterization of 3T3L1 EVs identified perilipin A in their composition. • Circulating EVs are elevated in obese mice and associated with glucose intolerance. • Circulating EVs are elevated in obese human and correlated with metabolic factors. • Perilipin A and EV levels are increased in the circulation of obese mice and human. • Circulating EV and perilipin A levels decrease with low calorie intervention.
KW - Adipocyte stress and hypertrophy
KW - Extracellular vesicles
KW - Noninvasive biomarker
KW - Obesity
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U2 - 10.1007/s00109-016-1446-8
DO - 10.1007/s00109-016-1446-8
M3 - Article
C2 - 27394413
AN - SCOPUS:84978153365
SN - 0946-2716
VL - 94
SP - 1241
EP - 1253
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
IS - 11
ER -