Exosomes participate in the alteration of muscle homeostasis during lipid-induced insulin resistance in mice

Abstract

Aims/hypothesisExosomes released from cells can transfer both functional proteins and RNAs between cells. In this study we tested the hypothesis that muscle cells might transmit specific signals during lipid-induced insulin resistance through the exosomal route.MethodsExosomes were collected from quadriceps muscles of C57Bl/6 mice fed for 16 weeks with either a standard chow diet (SD) or an SD enriched with 20% palm oil (HP) and from C2C12 cells exposed to 0.5 mmol/l palmitate (EXO-Post Palm), oleate (EXO-Post Oleate) or BSA (EXO-Post BSA).ResultsHP-fed mice were obese and insulin resistant and had altered insulin-induced Akt phosphorylation in skeletal muscle (SkM). They also had reduced expression of Myod1 and Myog and increased levels of Ccnd1 mRNA, indicating that palm oil had a deep impact on SkM homeostasis in addition to insulin resistance. HP-fed mouse SkM secreted more exosomes than SD-fed mouse SkM. This was reproduced in-vitro using C2C12 cells pre-treated with palmitate, the most abundant saturated fatty acid of palm oil. Exosomes from HP-fed mice, EXO-Post Palm and EXO-Post Oleate induced myoblast proliferation and modified the expressions of genes involved in the cell cycle and muscle differentiation but did not alter insulin-induced Akt phosphorylation. Lipidomic analyses showed that exosomes from palmitate-treated cells were enriched in palmitate, indicating that exosomes likely transfer the deleterious effect of palm oil between muscle cells by transferring lipids. Muscle exosomes were incorporated into various tissues in vivo, including the pancreas and liver, suggesting that SkM could transfer specific signals through the exosomal route to key metabolic tissues.Conclusions/interpretationExosomes act as ‘paracrine-like’ signals and modify muscle homeostasis during high-fat diets.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-014-3337-2) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Roles of Exosome-Like Vesicles Released from Inflammatory C2C12 Myotubes: Regulation of Myocyte Differentiation and Myokine Expression

“…6). In addition, the possibility that unidentified proteins, miRNAs, or lipids in ELVs from inflammatory myotubes regulating myogenesis and myokine expression could not be ruled out [56][57][58]. Interestingly, our results suggested that ELVs released from myotubes can contribute to the activation or maintenance of muscle differentiation [44]; however, ELVs from inflammatory myotubes might hinder the process of differentiation (Figs 5D and 6).…”

Cardiosome mediated regulation of MMP9 in diabetic heart: role of mir29b and mir455 in exercise

“…Another report by Aswad et al . (2014) suggests that in lipid induced insulin resistance mice, the muscle homeostasis is affected by exosomes . Hence, our findings on exosome mediated benefits of exercise in diabetic patients are novel.…”

Exosomes and diabetes

“…Accordingly, exosomes isolated from explants of the quadriceps muscle of mice challenged with a high palmitate diet induce myoblast replication and pancreatic β‐cell proliferation in vitro. These exosomes are enriched in miR‐16 , and this miRNA regulates the expression of genes involved in pancreas development, including proliferation suppressor protein patched homologue 1 (PTCH1) …”