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Multi\u2010nuclear MRS and MRI techniques have the potential to provide a comprehensive non\u2010invasive assessment of cardiac metabolic perturbation in obesity. A rat model of obesity was created by high\u2010fat diet feeding. This model was characterized using in vivo hyperpolarized [1\u2010<jats:sup>13<\/jats:sup>C]pyruvate and [2\u2010<jats:sup>13<\/jats:sup>C]pyruvate MRS, echocardiography and perfused heart <jats:sup>31<\/jats:sup>P MRS. Two groups of obese rats were subsequently treated with either caloric restriction or the glucagon\u2010like peptide\u20101 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 <jats:sup>13<\/jats:sup>C and <jats:sup>31<\/jats:sup>P 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 \u0394<jats:italic>G<\/jats:italic><jats:sub>~ATP<\/jats:sub>). 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 <jats:sup>13<\/jats:sup>C and <jats:sup>31<\/jats:sup>P MRS demonstrated abnormalities in cardiac metabolism at multiple levels, including myocardial substrate selection, TCA cycle, and high\u2010energy 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 <jats:sup>13<\/jats:sup>C and <jats:sup>31<\/jats:sup>P techniques now available for human use, the findings support a role for multi\u2010nuclear MRS in the development of new therapies for obesity.<\/jats:p>","DOI":"10.1002\/nbm.5206","type":"journal-article","created":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T06:35:28Z","timestamp":1720766128000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Hyperpolarized <sup>13<\/sup>C and <sup>31<\/sup>P MRS detects differences in cardiac energetics, metabolism, and function in obesity, and responses following treatment"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3714-6711","authenticated-orcid":false,"given":"Andrew J. 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