Immature adipocyte‐derived exosomes inhibit expression of muscle differentiation markers

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