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

Aguer C, Foretz M, Lantier L, Hebrard S, Viollet B, Mercier J, Kitzmann M
PLoS One. 2011 6 (12): e28981

PMID: 22194967 · PMCID: PMC3241688 · DOI:10.1371/journal.pone.0028981

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.

MeSH Terms (16)

Aminoimidazole Carboxamide AMP-Activated Protein Kinases Cadherins Cell Differentiation Diabetes Mellitus, Type 2 Endocytosis Enzyme Activation Humans Insulin Lipid Metabolism Membrane Microdomains Middle Aged Muscle Fibers, Skeletal Oxidation-Reduction Protein Transport Ribonucleotides

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