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Monitoring acute metabolic changes in the liver and kidneys induced by fructose and glucose using hyperpolarized [2-13 C]dihydroxyacetone.

ABSTRACT: To investigate acute changes in glucose metabolism in liver and kidneys in vivo after a bolus injection of either fructose or glucose, using hyperpolarized [2-13 C]dihydroxyacetone.Spatially registered, dynamic, multislice MR spectroscopy was acquired for the metabolic products of [2-13 C]dihydroxyacetone in liver and kidneys. Metabolism was probed in 13 fasted rats at three time points: 0, 70, and 140?min. At 60?min, rats were injected intravenously with fructose (n?=?5) or glucose (n?=?4) at 0.8?g/kg to initiate acute response. Controls (n?=?4) did not receive a carbohydrate challenge.Ten minutes after fructose infusion, levels of [2-13 C]phosphoenolpyruvate and [2-13 C]glycerol-3-phosphate halved in liver: 51% (P?=?0.0010) and 47% (P?=?0.0001) of baseline, respectively. Seventy minutes later, levels returned to baseline. The glucose challenge did not alter the signals significantly, nor did repeated administration of the dihydroxyacetone imaging bolus. In kidneys, no statistically significant changes were detected after sugar infusion other than a 20% increase of the glycerol-3-phosphate signal between 10 and 80?min after fructose injection (P?=?0.0028).Hyperpolarized [2-13 C]dihydroxyacetone detects a real-time, transient metabolic response of the liver to an acute fructose challenge. Observed effects possibly include ATP depletion and changes in the unlabeled pool sizes of glycolytic intermediates. Magn Reson Med 77:65-73, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

SUBMITTER: Marco-Rius I

PROVIDER: S-EPMC5191913 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Monitoring acute metabolic changes in the liver and kidneys induced by fructose and glucose using hyperpolarized [2-<sup>13</sup> C]dihydroxyacetone.

Marco-Rius Irene I von Morze Cornelius C Sriram Renuka R Cao Peng P Chang Gene-Yuan GY Milshteyn Eugene E Bok Robert A RA Ohliger Michael A MA Pearce David D Kurhanewicz John J Larson Peder E Z PE Vigneron Daniel B DB Merritt Matthew M

Magnetic resonance in medicine 20161117 1

<h4>Purpose</h4>To investigate acute changes in glucose metabolism in liver and kidneys in vivo after a bolus injection of either fructose or glucose, using hyperpolarized [2-<sup>13</sup> C]dihydroxyacetone.<h4>Methods</h4>Spatially registered, dynamic, multislice MR spectroscopy was acquired for the metabolic products of [2-<sup>13</sup> C]dihydroxyacetone in liver and kidneys. Metabolism was probed in 13 fasted rats at three time points: 0, 70, and 140 min. At 60 min, rats were injected intra ...[more]

PMID: 27859575

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Project description:With signal-to-noise ratio enhancements on the order of 10,000-fold, hyperpolarized MRSI of metabolically active substrates allows the study of both the injected substrate and downstream metabolic products in vivo. Although hyperpolarized [1-(13)C]pyruvate, in particular, has been used to demonstrate metabolic activities in various animal models, robust quantification and metabolic modeling remain important areas of investigation. Enzyme saturation effects are routinely seen with commonly used doses of hyperpolarized [1-(13)C]pyruvate; however, most metrics proposed to date, including metabolite ratios, time-to-peak of metabolic products and single exchange rate constants, fail to capture these saturation effects. In addition, the widely used small-flip-angle excitation approach does not correctly model the inflow of fresh downstream metabolites generated proximal to the target slice, which is often a significant factor in vivo. In this work, we developed an efficient quantification framework employing a spiral-based dynamic spectroscopic imaging approach. The approach overcomes the aforementioned limitations and demonstrates that the in vivo (13)C labeling of lactate and alanine after a bolus injection of [1-(13)C]pyruvate is well approximated by saturatable kinetics, which can be mathematically modeled using a Michaelis-Menten-like formulation, with the resulting estimated apparent maximal reaction velocity V(max) and apparent Michaelis constant K(M) being unbiased with respect to critical experimental parameters, including the substrate dose, bolus shape and duration. Although the proposed saturatable model has a similar mathematical formulation to the original Michaelis-Menten kinetics, it is conceptually different. In this study, we focus on the (13)C labeling of lactate and alanine and do not differentiate the labeling mechanism (net flux or isotopic exchange) or the respective contribution of various factors (organ perfusion rate, substrate transport kinetics, enzyme activities and the size of the unlabeled lactate and alanine pools) to the labeling process.

Dataset Information

Monitoring acute metabolic changes in the liver and kidneys induced by fructose and glucose using hyperpolarized [2-13 C]dihydroxyacetone.

Publications

Monitoring acute metabolic changes in the liver and kidneys induced by fructose and glucose using hyperpolarized [2-<sup>13</sup> C]dihydroxyacetone.

Similar Datasets

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