In vivo absolute quantification of hepatic γ‐ATP concentration in mice using 31P MRS at 11.7 T. (6th October 2020)

• Record Type: Journal Article
• Authors: Rothe, Maik; Wessel, Corinna; Cames, Sandra; Szendroedi, Julia; Burkart, Volker; Hwang, Jong‐Hee; Roden, Michael
• Is Part Of: NMR in biomedicine. Volume 34:Number 2(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-10-06
• Subjects: diabetes -- hepatobiliary system -- mitochondrial function -- mouse -- obesity -- phosphorus MRS/MRSI -- spectroscopic quantification; Nuclear magnetic resonance -- Periodicals; Magnetic Resonance Spectroscopy -- Periodicals; 574
• DOI: 10.1002/nbm.4422
• Languages: English
• ISSNs: 0952-3480

Abstract

Abstract : 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. Abstract : A fast and robust single voxel 31 P MRS method was established to quantify hepatic γ‐ATP concentrations at 11.7 T in three mouse models with various insulin sensitivities and liver fat contents. Absolute quantification was performed by employing an external reference and a matching replacement ATP phantom with 3D ISIS in 17 min. Abnormal hepatic energy metabolism in mice with insulin resistance and non‐alcoholic fatty liver disease was detected, suggesting further applications of the current method in other mouse model studies.