title: Exosomes participate in the alteration of muscle homeostasis during lipid-induced insulin resistance in mice.
abstract: OBJECTIVE
  Exosomes 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.
  
  
  METHODS
  Exosomes 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).
  
  
  RESULTS
  HP-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
  Exosomes act as 'paracrine-like' signals and modify muscle homeostasis during high-fat diets.
authors: CarMeN Laboratory (Inserm 1060, INRA 1397, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Oullins, France.
authors: Hala
authors: H
authors: Aswad
authors: Alexis
authors: A
authors: Forterre
authors: Oscar P B
authors: OP
authors: Wiklander
authors: Guillaume
authors: G
authors: Vial
authors: Emmanuelle
authors: E
authors: Danty-Berger
authors: Audrey
authors: A
authors: Jalabert
authors: Antonin
authors: A
authors: Lamazière
authors: Emmanuelle
authors: E
authors: Meugnier
authors: Sandra
authors: S
authors: Pesenti
authors: Catherine
authors: C
authors: Ott
authors: Karim
authors: K
authors: Chikh
authors: Samir
authors: S
authors: El-Andaloussi
authors: Hubert
authors: H
authors: Vidal
authors: Etienne
authors: E
authors: Lefai
authors: Jennifer
authors: J
authors: Rieusset
authors: Sophie
authors: S
authors: Rome
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D055354:Exosomes / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology; D010168:Palmitates / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D010168:Palmitates; D019301:Oleic Acid