title: Increased FAT/CD36 cycling and lipid accumulation in myotubes derived from obese type 2 diabetic patients.
abstract: BACKGROUND
  Permanent fatty acid translocase (FAT/)CD36 relocation has previously been shown to be related to abnormal lipid accumulation in the skeletal muscle of type 2 diabetic patients, however mechanisms responsible for the regulation of FAT/CD36 expression and localization are not well characterized in human skeletal muscle.
  
  
  RESULTS
  Primary muscle cells derived from obese type 2 diabetic patients (OBT2D) and from healthy subjects (Control) were used to examine the regulation of FAT/CD36. We showed that compared to Control myotubes, FAT/CD36 was continuously cycling between intracellular compartments and the cell surface in OBT2D myotubes, independently of lipid raft association, leading to increased cell surface FAT/CD36 localization and lipid accumulation. Moreover, we showed that FAT/CD36 cycling and lipid accumulation were specific to myotubes and were not observed in reserve cells. However, in Control myotubes, the induction of FAT/CD36 membrane translocation by the activation of (AMP)-activated protein kinase (AMPK) pathway did not increase lipid accumulation. This result can be explained by the fact that pharmacological activation of AMPK leads to increased mitochondrial beta-oxidation in Control cells.
  
  
  CONCLUSIONS
  Lipid accumulation in myotubes derived from obese type 2 diabetic patients arises from abnormal FAT/CD36 cycling while lipid accumulation in Control cells results from an equilibrium between lipid uptake and oxidation. As such, inhibiting FAT/CD36 cycling in the skeletal muscle of obese type 2 diabetic patients should be sufficient to diminish lipid accumulation.
authors.affiliation: INSERM, U1046 Physiologie et Médecine Expérimentale du Cœur et des Muscles, Montpellier, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Aguer
authors.forename: Marc
authors.initials: M
authors.lastname: Foretz
authors.forename: Louise
authors.initials: L
authors.lastname: Lantier
authors.forename: Sophie
authors.initials: S
authors.lastname: Hebrard
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.forename: Jacques
authors.initials: J
authors.lastname: Mercier
authors.forename: Magali
authors.initials: M
authors.lastname: Kitzmann
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology*; D004705:Endocytosis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012265:Ribonucleotides / Q000494:pharmacology
chemical_list: D015820:Cadherins; C502403:FAT1 protein, human; D007328:Insulin; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide