In Vivo Absolute Quantification Of Hepatic Gamma-Atp Concentration In Mice Using(31)P Mrs At 11.7 T

Measurement of ATP concentrations and synthesis in humans indicated abnormal hepatic energy metabolism in obesity, non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes. Further mechanistic studies on energy metabolism require the detailed phenotyping of specific mouse models. Thus, this study aimed to establish and evaluate a robust and fast single voxel(31)P MRS method to quantify hepatic gamma-ATP concentrations at 11.7 T in three mouse models with different insulin sensitivities and liver fat contents (72-week-old C57BL/6 control mice, 72-week-old insulin resistant sterol regulatory-element binding protein-1c overexpressing (SREBP-1c(+)) mice and 10-12-week-old prediabetic non-obese diabetic (NOD) mice). Absolute quantification was performed by employing an external reference and a matching replacement ATP phantom with 3D image selected in vivo spectroscopy(31)P MRS. This single voxel(31)P MRS method non-invasively quantified hepatic gamma-ATP within 17 min and the repeatability tests provided a coefficient of variation of 7.8 +/- 1.1%. The mean hepatic gamma-ATP concentrations were markedly lower in SREBP-1c(+)mice (1.14 +/- 0.10 mM) than in C57BL/6 mice (2.15 +/- 0.13 mM;p< 0.0002) and NOD mice (1.78 +/- 0.13 mM;p< 0.006, one-way ANOVA test). In conclusion, this method allows us to rapidly and precisely measure hepatic gamma-ATP concentrations, and thereby to non-invasively detect abnormal hepatic energy metabolism in mice with different degrees of insulin resistance and NAFLD. Thus, this(31)P MRS will also be useful for future mechanistic as well as therapeutic translational studies in other murine models.