Increased FAT/CD36 cycling and lipid accumulation in myotubes derived from obese type 2 diabetic patients

PLoS One. 2011;6(12):e28981. doi: 10.1371/journal.pone.0028981. Epub 2011 Dec 16.

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.

Methodology/principal findings: 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.

Conclusion/significance: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Cadherins / metabolism*
  • Cell Differentiation / drug effects
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / pathology*
  • Endocytosis* / drug effects
  • Enzyme Activation / drug effects
  • Humans
  • Insulin / pharmacology
  • Lipid Metabolism* / drug effects
  • Membrane Microdomains / drug effects
  • Membrane Microdomains / metabolism
  • Middle Aged
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / enzymology
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle Fibers, Skeletal / pathology
  • Oxidation-Reduction / drug effects
  • Protein Transport / drug effects
  • Ribonucleotides / pharmacology

Substances

  • Cadherins
  • FAT1 protein, human
  • Insulin
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide