In vivo absolute quantification of hepatic γ‐ATP concentration in mice using 31P MRS at 11.7 T,NMR in Biomedicine

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In vivo absolute quantification of hepatic γ‐ATP concentration in mice using 31P MRS at 11.7 T
NMR in Biomedicine ( IF 2.7 ) Pub Date : 2020-10-06 , DOI: 10.1002/nbm.4422
Maik Rothe _{1,

2} , Corinna Wessel _{1,

2} , Sandra Cames _{1,

2} , Julia Szendroedi _{1,

2,

3} , Volker Burkart _{1,

2} , Jong-Hee Hwang _{1,

2} , Michael Roden _{1,

2,

3}

Affiliation

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 ³¹P 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 ³¹P MRS. This single voxel ³¹P 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 ³¹P MRS will also be useful for future mechanistic as well as therapeutic translational studies in other murine models.

中文翻译：

使用 11.7 T 的 31P MRS 对小鼠肝脏 γ-ATP 浓度的体内绝对定量

人体 ATP 浓度和合成的测量表明肥胖、非酒精性脂肪肝 (NAFLD) 和 2 型糖尿病患者的肝脏能量代谢异常。对能量代谢的进一步机制研究需要对特定小鼠模型进行详细的表型分析。因此，本研究旨在建立和评估一种稳健且快速的单体素³¹ P MRS 方法，以在具有不同胰岛素敏感性和肝脏脂肪含量的三种小鼠模型（72 周龄 C57BL/6对照小鼠，72 周龄胰岛素抵抗甾醇调节元件结合蛋白-1c 过表达（SREBP-1c ⁺) 小鼠和 10-12 周龄的糖尿病前期非肥胖糖尿病 (NOD) 小鼠）。通过使用外部参考和匹配的替换 ATP 体模与 3D 图像进行绝对量化，该 3D 图像在体内光谱³¹ P MRS 中选择。这种单体素³¹ P MRS 方法在 17 分钟内无创量化了肝脏 γ-ATP，重复性测试提供了 7.8 ± 1.1% 的变异系数。SREBP-1c ⁺小鼠 (1.14 ± 0.10 mM)的平均肝脏 γ-ATP 浓度明显低于C57BL/6 小鼠 (2.15 ± 0.13 mM; p < 0.0002) 和 NOD 小鼠 (1.78 ± 0.13 mM; p< 0.006，单向方差分析测试）。总之，该方法使我们能够快速准确地测量肝脏 γ-ATP 浓度，从而无创地检测具有不同程度胰岛素抵抗和 NAFLD 的小鼠肝脏能量代谢异常。因此，这个³¹ P MRS 也将用于其他小鼠模型中未来的机械和治疗转化研究。

更新日期：2020-10-06

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