Hyperpolarized 13C and 31P MRS detects differences in cardiac energetics, metabolism, and function in obesity, and responses following treatment

Andrew J. M. Lewis, Michael Dodd, Joevin Sourdon, Craig A. Lygate, Kieran Clarke, Stefan Neubauer, Damian J Tyler, Oliver J. Rider

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Abstract

Obesity is associated with important changes in cardiac energetics and function, and an increased risk of adverse cardiovascular outcomes. Multi-nuclear MRS and MRI techniques have the potential to provide a comprehensive non-invasive assessment of cardiac metabolic perturbation in obesity. A rat model of obesity was created by high-fat diet feeding. This model was characterized using in vivo hyperpolarized [1-13C]pyruvate and [2-13C]pyruvate MRS, echocardiography and perfused heart 31P MRS. Two groups of obese rats were subsequently treated with either caloric restriction or the glucagon-like peptide-1 analogue/agonist liraglutide, prior to reassessment. The model recapitulated cardiovascular consequences of human obesity, including mild left ventricular hypertrophy, and diastolic, but not systolic, dysfunction. Hyperpolarized 13C and 31P MRS demonstrated that obesity was associated with reduced myocardial pyruvate dehydrogenase flux, altered cardiac tricarboxylic acid (TCA) cycle metabolism, and impaired myocardial energetic status (lower phosphocreatine to adenosine triphosphate ratio and impaired cardiac ΔG~ATP). Both caloric restriction and liraglutide treatment were associated with normalization of metabolic changes, alongside improvement in cardiac diastolic function. In this model of obesity, hyperpolarized 13C and 31P MRS demonstrated abnormalities in cardiac metabolism at multiple levels, including myocardial substrate selection, TCA cycle, and high-energy phosphorus metabolism. Metabolic changes were linked with impairment of diastolic function and were reversed in concert following either caloric restriction or liraglutide treatment. With hyperpolarized 13C and 31P techniques now available for human use, the findings support a role for multi-nuclear MRS in the development of new therapies for obesity.
Original languageEnglish
Article numbere5206
Pages (from-to)(In-Press)
Number of pages10
JournalNMR in Biomedicine
Volume37
Issue number11
Early online date12 Jul 2024
DOIs
Publication statusE-pub ahead of print - 12 Jul 2024

Bibliographical note

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Funder

Funded by the Academy of Medical Sciences and the British Heart Foundation (RG/13/8/30266 and RG/18/12/34040 to SN and CL, FS/14/17/30634 and FS/19/18/34252 to DJT). AL acknowledges the funding (or) support of the NIHR Oxford Biomedical Research Centre and the BHF Oxford Centre for Research Excellence RE/18/3/34214.

Keywords

  • diastolic function
  • hyperpolarized MRI
  • obesity

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