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
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 a...
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Nature Portfolio
2021
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oai:doaj.org-article:77abc8f4de834fbea9f2c2609f3647542021-11-08T10:46:15ZProfiling of ob/ob mice skeletal muscle exosome-like vesicles demonstrates combined action of miRNAs, proteins and lipids to modulate lipid homeostasis in recipient cells10.1038/s41598-021-00983-32045-2322https://doaj.org/article/77abc8f4de834fbea9f2c2609f3647542021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-00983-3https://doaj.org/toc/2045-2322Abstract 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.Audrey JalabertLaura ReiningerEmmanuelle BergerYohann CouteEmmanuelle MeugnierAlexis ForterreElizabeth Errazuriz-CerdaAlain GeloenMyriam AouadiKarim BouzakriJennifer RieussetSophie RomeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021) |
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Medicine R Science Q |
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Medicine R Science Q Audrey Jalabert Laura Reininger Emmanuelle Berger Yohann Coute Emmanuelle Meugnier Alexis Forterre Elizabeth Errazuriz-Cerda Alain Geloen Myriam Aouadi Karim Bouzakri Jennifer Rieusset Sophie Rome 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 |
| description |
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. |
| format |
article |
| author |
Audrey Jalabert Laura Reininger Emmanuelle Berger Yohann Coute Emmanuelle Meugnier Alexis Forterre Elizabeth Errazuriz-Cerda Alain Geloen Myriam Aouadi Karim Bouzakri Jennifer Rieusset Sophie Rome |
| author_facet |
Audrey Jalabert Laura Reininger Emmanuelle Berger Yohann Coute Emmanuelle Meugnier Alexis Forterre Elizabeth Errazuriz-Cerda Alain Geloen Myriam Aouadi Karim Bouzakri Jennifer Rieusset Sophie Rome |
| author_sort |
Audrey Jalabert |
| title |
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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/77abc8f4de834fbea9f2c2609f364754 |
| work_keys_str_mv |
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1718442629313593344 |