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, 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.
Subject(s)
CD36 Antigens/metabolism , Diabetes Mellitus, Type 2/metabolism , Lipids/analysis , Muscle, Skeletal/chemistry , Obesity/metabolism , AMP-Activated Protein Kinases/metabolism , Acetyl-CoA Carboxylase/metabolism , Analysis of Variance , Blotting, Western , Body Fat Distribution , Cells, Cultured , Citrate (si)-Synthase/metabolism , Diabetes Mellitus, Type 2/complications , Fluorescent Antibody Technique , Humans , Male , Middle Aged , Mitochondria/metabolism , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism , Obesity/complications , Phosphorylation/physiology , Waist CircumferenceABSTRACT
During the past decade, several studies have reported positive effects of cognitive-behavioral therapy (CBT) in the treatment of children and adolescents with mental disorders. One of the most important CBT interventions is to teach children and adolescents to challenge negative thoughts that lead to maladjusted behaviors. Based on the implicit theories of intelligence framework, the main purpose of this study was to test whether an incremental theory manipulation could be used to affect IQ test performance in adolescents with Generalized Anxiety Disorder (GAD). Results showed that patients demonstrated enhanced IQ performance and experienced less state anxiety when they were exposed to an incremental theory of intelligence manipulation. Our findings suggest that incremental theory manipulation provides a useful cognitive strategy for addressing school-related anxiety in adolescents with mental disorders such as GAD.
