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

Abstract

BackgroundOne 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 2H‐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.PurposeEvaluating the feasibility of DMI as a tool for the assessment of metabolic differences in rodents with healthy and fatty livers (FLs).Study TypeAnimal Model.Population18 male Sprague Dawley rats on standard (SD, n = 9, healthy) and high‐fat diet (HFD, n = 9, FL disease).Field Strength/SequencePhase‐encoded 1D pulse‐acquire sequence and anatomy co‐registered phase‐encoded 3D pulse‐acquire chemical shift imaging for 2H at 9.4T.AssessmentLocalized 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 2H natural abundance water peak.Statistical TestsTwo‐way repeated measures ANOVA were employed to assess between‐group differences, with statistical significance at P < 0.05.ResultsDMI measurements demonstrated no significant difference (P = 0.98) in the uptake of [6,6′‐2H2]glucose between healthy and impaired animals (AUCSD = 1966.0 ± 151.5 mM ‐ minutes vs. AUCHFD = 2027.0 ± 167.6 mM·minutes). In the diseased group, the intrahepatic uptake of palmitic acid d‐31 was higher (AUCHFD = 57.4 ± 17.0 mM·minutes, AUCSD = 33.3 ± 10.5 mM·minutes), but without statistical significance owing to substantial in‐group variation (P = 0.73).Data ConclusionDMI 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 Evidence2Technical EfficacyStage 3.