Immature adipocyte-derived exosomes inhibit expression of muscle differentiation markers

FEBS Open Bio. 2021 Mar;11(3):768-781. doi: 10.1002/2211-5463.13100. Epub 2021 Feb 16.

Abstract

Exosomes are released from a variety of cells to communicate with recipient cells. Exosomes contain microRNAs (miRNAs), which are noncoding RNAs that suppress target genes. Our previous proteomic study (FEBS Open Bio 2016, 6, 816-826) demonstrated that 3T3-L1 adipocytes secrete exosome components as well as growth factors, inspiring us to investigate what type of miRNA is involved in adipocyte-secreted exosomes and what functions they carry out in recipient cells. Here, we profiled miRNAs in 3T3-L1 adipocyte-secreted exosomes and revealed suppression of muscle differentiation by adipocyte-derived exosomes. Through our microarray analysis, we detected over 300 exosomal miRNAs during adipocyte differentiation. Exosomal miRNAs present during adipocyte differentiation included not only pro-adipogenic miRNAs but also miRNAs associated with muscular dystrophy. Gene ontology analysis predicted that the target genes of miRNAs are associated primarily with transcriptional regulation. To further investigate whether adipocyte-secreted exosomes regulate the expression levels of genes involved in muscle differentiation, we treated cultured myoblasts with adipocyte-derived exosome fractions. Intriguingly, the expression levels of myogenic regulatory factors, Myog and Myf6, and other muscle differentiation markers, myosin heavy-chain 3 and insulin-like growth factor 2, were significantly downregulated in myoblasts treated with adipocyte-derived exosomes. Immature adipocyte-derived exosomes exhibited a stronger suppressive effect than mature adipocyte-derived exosomes. Our results suggest that adipocytes suppress the expression levels of muscle differentiation-associated genes in myoblasts via adipocyte-secreted exosomes containing miRNAs.

Keywords: adipocyte; exosome; miRNA; muscular dystrophy; skeletal muscle.

Associated data

  • RefSeq/NM_009605
  • RefSeq/NM_010514
  • RefSeq/NM_010866
  • RefSeq/NM_031189
  • RefSeq/NM_008656
  • RefSeq/NM_008657
  • RefSeq/NM_001099635
  • RefSeq/NM_001006345