Intramyocellular lipid accumulation is associated with permanent relocation ex vivo and in vitro of fatty acid translocase (FAT)/CD36 in obese patients

authors

  • Aguer C
  • Mercier Jacques
  • Yong Wai Man C
  • Metz L.
  • Bordenave S.
  • Lambert Karen
  • Jean E
  • Lantier L
  • Bounoua L
  • Brun Jean-Frédéric
  • Raynaud E.
  • Andreelli F.
  • Foretz M
  • Kitzmann M

keywords

  • Type 2 diabetes
  • Obesity
  • Skeletal muscle
  • Human myotubes
  • Lipid

document type

ART

abstract

Aims/hypothesis Intramyocellular lipids (IMCL) accumulation is a classical feature of metabolic diseases. We hypothesised that IMCL accumulate mainly as a consequence of increased adiposity and independently of type 2 diabetes. To test this, we examined IMCL accumulation in two different models and four different populations of participants: muscle biopsies and primary human muscle cells derived from non-obese and obese participants with or without type 2 diabetes. The mechanism regulating IMCL accumulation was also studied. Methods Muscle biopsies were obtained from ten non-obese and seven obese participants without type 2 diabetes, and from eight non-obese and eight obese type 2 diabetic patients. Mitochondrial respiration, citrate synthase activity and both AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation were measured in muscle tissue. Lipid accumulation in muscle and primary myotubes was estimated by Oil Red O staining and fatty acid translocase (FAT)/CD36 localisation by immunofluorescence. Results Obesity and type 2 diabetes are independently characterised by skeletal muscle IMCL accumulation and permanent FAT/CD36 relocation. Mitochondrial function is not reduced in type 2 diabetes. IMCL accumulation was independent of type 2 diabetes in cultured myotubes and was correlated with obesity markers of the donor. In obese participants, membrane relocation of FAT/CD36 is a determinant of IMCL accumulation. Conclusions/interpretation In skeletal muscle, mitochon-drial function is normal in type 2 diabetes, while IMCL

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