In vivo absolute quantification of hepatic γ-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 γ-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 γ-ATP within 17 min and the repeatability tests provided a coefficient of variation of 7.8 ± 1.1%. The mean hepatic γ-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 γ-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.