1. 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
- Author
-
Sophie Rome, Myriam Aouadi, Karim Bouzakri, Laura Reininger, Emmanuelle Berger, Emmanuelle Meugnier, Alexis Forterre, Alain Géloën, Jennifer Rieusset, Elizabeth Errazuriz-Cerda, Yohann Couté, Audrey Jalabert, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Diabète et thérapies cellulaires (DIATHEC), Université de Strasbourg (UNISTRA), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), BioSanté (UMR BioSanté), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Université de Lyon, Karolinska Inst, Ctr Infect Med, Dept Med, Huddinge, Sweden, ANR-10-INBS-08, ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), Diabète et thérapeutique : îlots pancréatiques et innovations technologiques (DIATHEC), and Diabète et thérapies cellulaires
- Subjects
Male ,Proteome ,Science ,Adipose tissue ,Mice, Obese ,Muscle Proteins ,Exosomes ,Exosome ,Biochemistry ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Lipid oxidation ,medicine ,Myocyte ,Animals ,Homeostasis ,Muscle, Skeletal ,Beta oxidation ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Molecular medicine ,Chemistry ,Skeletal muscle ,Lipid metabolism ,Lipids ,Cell biology ,Mice, Inbred C57BL ,MicroRNAs ,Muscular Atrophy ,medicine.anatomical_structure ,Adipose Tissue ,Medicine ,Insulin Resistance ,Sphingomyelin ,030217 neurology & neurosurgery ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
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.
- Published
- 2021
- Full Text
- View/download PDF