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Hyperpolarized (HP) <jats:sup>13<\/jats:sup>C MRI provides a unique view of the metabolic microenvironment, with potential relevance for early diagnosis of liver disease. Previous studies have detected changes in HP <jats:sup>13<\/jats:sup>C pyruvate to lactate conversion, catalyzed by lactate dehydrogenase (LDH), with experimental liver injury. HP <jats:inline-formula><jats:alternatives><jats:tex-math>$$\\propto $$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                  <mml:mo>\u221d<\/mml:mo>\n                <\/mml:math><\/jats:alternatives><\/jats:inline-formula>-ketobutyrate (<jats:inline-formula><jats:alternatives><jats:tex-math>$$\\propto $$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                  <mml:mo>\u221d<\/mml:mo>\n                <\/mml:math><\/jats:alternatives><\/jats:inline-formula> KB) is a close molecular analog of pyruvate with modified specificity for LDH isoforms, specifically attenuated activity with their LDHA-expressed subunits that dominate liver parenchyma. Building on recent results with pyruvate, we investigated HP <jats:inline-formula><jats:alternatives><jats:tex-math>$$\\propto $$<\/jats:tex-math><mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\">\n                  <mml:mo>\u221d<\/mml:mo>\n                <\/mml:math><\/jats:alternatives><\/jats:inline-formula> KB in methionine-choline deficient (MCD) diet as a model of early-stage NASH. Similarity of results between this new agent and pyruvate (~\u200950% drop in cytoplasmic reducing capacity), interpreted together with gene expression data from the model, suggests that changes are mediated through broad effects on intermediary metabolism. Plausible mechanisms are depletion of the lactate pool by upregulation of gluconeogenesis (GNG) and pentose phosphate pathway (PPP) flux, and a possible shift toward increased lactate oxidation. These changes may reflect high levels of oxidative stress and\/or shifting macrophage populations in NASH.<\/jats:p>","DOI":"10.1038\/s41598-024-65951-z","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T14:04:52Z","timestamp":1719497092000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Detection of early-stage NASH using non-invasive hyperpolarized 13C metabolic imaging"],"prefix":"10.1038","volume":"14","author":[{"given":"Cornelius","family":"von Morze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Blazey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Spees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kooresh I.","family":"Shoghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Ohliger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"issue":"9","key":"65951_CR1","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","volume":"7","author":"K Riazi","year":"2022","unstructured":"Riazi, K. et al. 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