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Abstract #2630

AGAT-/- Mice: A Metabolic Puzzle of Energy Deficiency and Insulin Sensitivity

Patricia Maria Nunes1, Christine I. H. C. Nabuurs1, Dirk Isbrandt2, Cees Tack3, Arend Heerschap1

1Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 2Centre for Molecular Neurobiology, Institute for Signal Transduction, Hamburg, Germany; 3Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

Whole body creatine depletion causes several disarrangements in brain and muscle. In these conditions, AGAT-/-mice, a mouse model for deficient creatine biosynthesis, have enhanced food intake and permanent lower body weight which may reflect a higher substrate catabolism. We assessed ex vivo hepatic triglyceride concentration and the respective synthesis contributions from de novo lipogenesis (DNL) and dietary free fatty acids, by 1H / 2H-NMR. Additionally, we evaluated whole body glucose and insulin levels during a glucose tolerance test. Our results showed that AGAT-/- had lower hepatic triglycerides and the contribution from DNL, to this pool, was increased. On the contrary, dietary fatty acids contribute less to the hepatic triglyceride pool. This suggests that dietary fatty acids are preferentially recruited to high energy demanding tissues as muscle. These data matched with lower glucose and insulin concentrations during the glucose tolerance test, reflecting an insulin sensitive phenotype.