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.