Profiling of ob/ob mice skeletal muscle exosome-like vesicles demonstrates combined action of miRNAs, proteins and lipids to modulate lipid homeostasis in recipient cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Scientific Reports Année : 2021

Profiling of ob/ob mice skeletal muscle exosome-like vesicles demonstrates combined action of miRNAs, proteins and lipids to modulate lipid homeostasis in recipient cells

Laura Reininger
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Yohann Coute
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Karim Bouzakri
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Résumé

We have determined the lipid, protein and miRNA composition of skeletal muscle (SkM)-released extracellular vesicles (ELVs) from Ob/ob (OB) vs wild-type (WT) mice. The results showed that atrophic insulin-resistant OB-SkM released less ELVs than WT-SkM, highlighted by a RAB35 decrease and an increase in intramuscular cholesterol content. Proteomic analyses of OB-ELVs revealed a group of 37 proteins functionally connected, involved in lipid oxidation and with catalytic activities. OB-ELVs had modified contents for phosphatidylcholine (PC 34-4, PC 40-3 and PC 34-0), sphingomyelin (Sm d18:1/18:1) and ceramides (Cer d18:1/18:0) and were enriched in cholesterol, likely to alleviated intracellular accumulation. Surprisingly many ELV miRNAs had a nuclear addressing sequence, and targeted genes encoding proteins with nuclear activities. Interestingly, SkM-ELV miRNA did not target mitochondria. The most significant function targeted by the 7 miRNAs altered in OB-ELVs was lipid metabolism. In agreement, OB-ELVs induced lipid storage in recipient adipocytes and increased lipid up-take and fatty acid oxidation in recipient muscle cells. In addition, OB-ELVs altered insulin-sensitivity and induced atrophy in muscle cells, reproducing the phenotype of the releasing OB muscles. These data suggest for the first time, a cross-talk between muscle cells and adipocytes, through the SkM-ELV route, in favor of adipose tissue expansion.
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hal-03420029 , version 1 (08-11-2021)

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Audrey Jalabert, Laura Reininger, Emmanuelle Berger, Yohann Coute, Emmanuelle Meugnier, et al.. Profiling of ob/ob mice skeletal muscle exosome-like vesicles demonstrates combined action of miRNAs, proteins and lipids to modulate lipid homeostasis in recipient cells. Scientific Reports, 2021, 11 (1), ⟨10.1038/s41598-021-00983-3⟩. ⟨hal-03420029⟩
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