Circulating adipocyte-derived extracellular vesicles are novel markers of metabolic stress

Akiko Eguchi, Milos Lazic, Aaron M. Armando, Susan A. Phillips, Roia Katebian, Spyridoula Maraka, Oswald Quehenberger, Dorothy D. Sears, Ariel E. Feldstein

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1241-1253
Number of pages13
JournalJournal of Molecular Medicine
Volume94
Issue number11
DOIs
StatePublished - Nov 1 2016
Externally publishedYes

Fingerprint

Physiological Stress
Adipocytes
Obese Mice
Diet
Obesity
Extracellular Vesicles
Biomarkers
Glucose Intolerance
Macrophage Activation
Perilipin-1
Differentiation Antigens
Insulin Resistance
Adipose Tissue

Keywords

  • Adipocyte stress and hypertrophy
  • Extracellular vesicles
  • Noninvasive biomarker
  • Obesity

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Cite this

Eguchi, A., Lazic, M., Armando, A. M., Phillips, S. A., Katebian, R., Maraka, S., ... Feldstein, A. E. (2016). Circulating adipocyte-derived extracellular vesicles are novel markers of metabolic stress. Journal of Molecular Medicine, 94(11), 1241-1253. https://doi.org/10.1007/s00109-016-1446-8

Circulating adipocyte-derived extracellular vesicles are novel markers of metabolic stress. / Eguchi, Akiko; Lazic, Milos; Armando, Aaron M.; Phillips, Susan A.; Katebian, Roia; Maraka, Spyridoula; Quehenberger, Oswald; Sears, Dorothy D.; Feldstein, Ariel E.

In: Journal of Molecular Medicine, Vol. 94, No. 11, 01.11.2016, p. 1241-1253.

Research output: Contribution to journalArticle

Eguchi, A, Lazic, M, Armando, AM, Phillips, SA, Katebian, R, Maraka, S, Quehenberger, O, Sears, DD & Feldstein, AE 2016, 'Circulating adipocyte-derived extracellular vesicles are novel markers of metabolic stress', Journal of Molecular Medicine, vol. 94, no. 11, pp. 1241-1253. https://doi.org/10.1007/s00109-016-1446-8
Eguchi, Akiko ; Lazic, Milos ; Armando, Aaron M. ; Phillips, Susan A. ; Katebian, Roia ; Maraka, Spyridoula ; Quehenberger, Oswald ; Sears, Dorothy D. ; Feldstein, Ariel E. / Circulating adipocyte-derived extracellular vesicles are novel markers of metabolic stress. In: Journal of Molecular Medicine. 2016 ; Vol. 94, No. 11. pp. 1241-1253.
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abstract = "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.",
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AU - Katebian, Roia

AU - Maraka, Spyridoula

AU - Quehenberger, Oswald

AU - Sears, Dorothy D.

AU - Feldstein, Ariel E.

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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.

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