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

• Published in: Diabetologia 2010-06, Vol.53 (6), p.1151-1163
• Main Authors: Aguer, C, Mercier, J, Yong Wai Man, C, Metz, L, Bordenave, S, Lambert, K, Jean, E, Lantier, L, Bounoua, L, Brun, J. F, Raynaud de Mauverger, E, Andreelli, F, Foretz, M, Kitzmann, M
• Format: Article
• Language: English
• Subjects: Acetyl-CoA Carboxylase - metabolism; AMP-Activated Protein Kinases - metabolism; Analysis of Variance; Biological and medical sciences; Biopsy; Blotting, Western; Body Fat Distribution; CD36 Antigens - metabolism; Cells, Cultured; Citrate (si)-Synthase - metabolism; Cognitive science; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exercise; Fatty acids; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Human myotubes; Human Physiology; Humans; Internal Medicine; Kinases; Lipids; Lipids - analysis; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolism; Middle Aged; Mitochondria - metabolism; Muscle, Skeletal - chemistry; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Musculoskeletal system; noninsulin-dependent diabetes mellitus; Obesity; Obesity - complications; Obesity - metabolism; Oxidation; Phosphorylation - physiology; Proteins; Psychology; Respiration; skeletal muscle; Striated muscle. Tendons; Vertebrates: osteoarticular system, musculoskeletal system; Waist Circumference
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-010-1708-x

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, mitochondrial function is normal in type 2 diabetes, while IMCL accumulation is dependent upon obesity or type 2 diabetes and is related to sarcolemmal FAT/CD36 relocation. In cultured myotubes, IMCL content and FAT/CD36 relocation are independent of type 2 diabetes, suggesting that distinct factors in obesity and type 2 diabetes contribute to permanent FAT/CD36 relocation ex vivo.