使用氘代谢成像评估高脂饮食啮齿动物的肝脏葡萄糖和棕榈酸代谢

Evaluation of Hepatic Glucose and Palmitic Acid Metabolism in Rodents on High-Fat Diet Using Deuterium Metabolic Imaging.

作者信息

Ehret Viktoria, Ustsinau Usevalad, Friske Joachim, Scherer Thomas, Fürnsinn Clemens, Helbich Thomas H, Philippe Cécile, Krššák Martin

机构信息

Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria.

Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.

出版信息

J Magn Reson Imaging. 2025 Feb;61(2):958-967. doi: 10.1002/jmri.29437. Epub 2024 May 9.

DOI:10.1002/jmri.29437

PMID:38721871

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11706318/

Abstract

BACKGROUND

One of the main features of several metabolic disorders is dysregulation of hepatic glucose and lipid metabolism. Deuterium metabolic imaging (DMI) allows for assessing the uptake and breakdown of H-labeled substrates, giving specific insight into nutrient processing in healthy and diseased organs. Thus, DMI could be a useful approach for analyzing the differences in liver metabolism of healthy and diseased subjects to gain a deeper understanding of the alterations related to metabolic disorders.

PURPOSE

Evaluating the feasibility of DMI as a tool for the assessment of metabolic differences in rodents with healthy and fatty livers (FLs).

STUDY TYPE

Animal Model.

POPULATION

18 male Sprague Dawley rats on standard (SD, n = 9, healthy) and high-fat diet (HFD, n = 9, FL disease).

FIELD STRENGTH/SEQUENCE: Phase-encoded 1D pulse-acquire sequence and anatomy co-registered phase-encoded 3D pulse-acquire chemical shift imaging for H at 9.4T.

ASSESSMENT

Localized and nonlocalized liver spectroscopy was applied at eight time points over 104 minutes post injection. The obtained spectra were preprocessed and quantified using jMRUI (v7.0) and the resulting amplitudes translated to absolute concentration (mM) according to the H natural abundance water peak.

STATISTICAL TESTS

Two-way repeated measures ANOVA were employed to assess between-group differences, with statistical significance at P < 0.05.

RESULTS

DMI measurements demonstrated no significant difference (P = 0.98) in the uptake of [6,6'-H]glucose between healthy and impaired animals (AUC = 1966.0 ± 151.5 mM - minutes vs. AUC = 2027.0 ± 167.6 mM·minutes). In the diseased group, the intrahepatic uptake of palmitic acid d-31 was higher (AUC = 57.4 ± 17.0 mM·minutes, AUC = 33.3 ± 10.5 mM·minutes), but without statistical significance owing to substantial in-group variation (P = 0.73).

DATA CONCLUSION

DMI revealed higher concentrations of palmitic acid in rats with FL disease and no difference in hepatic glucose concentration between healthy and impaired animals. Thus, DMI appears to be a useful tool for evaluating metabolism in rodents with FL disease.

LEVEL OF EVIDENCE

2 TECHNICAL EFFICACY: Stage 3.

摘要

背景

几种代谢紊乱的主要特征之一是肝脏葡萄糖和脂质代谢失调。氘代谢成像（DMI）可用于评估氢标记底物的摄取和分解，从而深入了解健康和患病器官中的营养物质处理情况。因此，DMI可能是一种有用的方法，用于分析健康和患病受试者肝脏代谢的差异，以更深入地了解与代谢紊乱相关的改变。

目的

评估DMI作为评估健康和脂肪肝（FL）啮齿动物代谢差异工具的可行性。

研究类型

动物模型。

研究对象

18只雄性斯普拉格-道利大鼠，分别给予标准饮食（SD，n = 9，健康）和高脂饮食（HFD，n = 9，FL疾病）。

场强/序列：9.4T下用于氢的相位编码一维脉冲采集序列和解剖学共配准相位编码三维脉冲采集化学位移成像。

评估

在注射后104分钟内的八个时间点进行局部和非局部肝脏波谱分析。使用jMRUI（v7.0）对获得的波谱进行预处理和定量，并根据氢的天然丰度水峰将所得振幅转换为绝对浓度（mM）。

统计检验

采用双向重复测量方差分析评估组间差异，P < 0.05具有统计学意义。

结果

DMI测量显示，健康和患病动物之间[6,6'-H]葡萄糖的摄取无显著差异（P = 0.98）（曲线下面积[AUC] = 1966.0 ± 151.5 mM·分钟 vs. AUC = 2027.0 ± 167.6 mM·分钟）。在患病组中，棕榈酸d-31的肝内摄取较高（AUC = 57.4 ± 17.0 mM·分钟，AUC = 33.3 ± 10.5 mM·分钟），但由于组内差异较大，无统计学意义（P = 0.73）。