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August 1, 2023Cell Reports63 citationsOpen Access

Extracellular vesicles are carriers of adiponectin with insulin-sensitizing and anti-inflammatory properties

ABAlexia BlandinJAJérémy AmosseJFJosy Froger

Key Result

Adiponectin-enriched small extracellular vesicles improved insulin sensitivity and reduced weight gain in high-fat-diet-fed mice, highlighting their metabolic benefits.

Structured PICO

P
Population
Preclinical models including cultured visceral adipose tissue, HepG2 cells, HEK293 cells, lean/obese (ob/ob) mice, high-fat diet (HFD)-fed mice, adiponectin KO mice, and human blood samples from healthy, overweight, and obese patients.
I
Intervention
Adoptive transfer of adiponectin-enriched small extracellular vesicles (sEVs) derived from lean visceral adipose tissue via repetitive intraperitoneal injections over 5 weeks
C
Comparator
Vehicle (NaCl) or sEVs derived from adiponectin knockout (AdpnKO) mice
O
Outcome
Weight gain, glucose tolerance, insulin sensitivity, and tissue inflammationsurrogate

Adipose tissue-derived small extracellular vesicles act as stable carriers of adiponectin in the blood, mediating its insulin-sensitizing and anti-inflammatory effects in vivo.

Limitations

  • NHS ester labeling might impact sEV protein structure and targeting
  • Saponin treatment may overestimate the adiponectin intravesicular pool

Abstract

Recent evidence supporting that adipose tissue (AT)-derived extracellular vesicles (EVs) carry an important part of the AT secretome led us to characterize the EV-adipokine profile. In addition to evidencing a high AT-derived EV secretion ability that is further increased by obesity, we identify enrichment of oligomeric forms of adiponectin in small EVs (sEVs). This adipokine is mainly distributed at the EV external surface as a result of nonspecific adsorption of soluble adiponectin. EVs also constitute stable conveyors of adiponectin in the blood circulation. Adiponectin-enriched sEVs display in vitro insulin-sensitizing effects by binding to regular adiponectin receptors. Adoptive transfer of adiponectin-enriched sEVs in high-fat-diet-fed mice prevents animals from gaining weight and ameliorated insulin resistance and tissue inflammation, with major effects observed in the AT and liver. Our results therefore provide information regarding adiponectin-related metabolic responses by highlighting EVs as delivery platforms of metabolically active forms of adiponectin molecules.

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Cite This Study

Blandin et al. (2023) studied this question. Adiponectin-enriched small extracellular vesicles improved insulin sensitivity and reduced weight gain in high-fat-diet-fed mice, highlighting their metabolic benefits.

synapsesocial.com/papers/69614a2e51e09f8b1e9b8435https://doi.org/10.1016/j.celrep.2023.112866
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