{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:47:06Z","timestamp":1792075626841,"version":"4.4.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1I1A1A01065063, 2021R1A2C2094512"],"award-info":[{"award-number":["2020R1I1A1A01065063, 2021R1A2C2094512"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) feature paradoxical increases in both gluconeogenesis and lipogenesis. ATP citrate lyase (ACLY) supports both processes by generating cytosolic acetyl-CoA and oxaloacetate from citrate. While ACLY\u2019s role in lipogenesis is well established, its involvement in amino acid\u2013driven gluconeogenesis remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Using hyperpolarized [1-\n                      <jats:sup>13<\/jats:sup>\n                      C]pyruvate magnetic resonance spectroscopy (MRS), we observed [1-\n                      <jats:sup>13<\/jats:sup>\n                      C]alanine labeling in the livers of db\/db mice. To test the effect of ACLY inhibition, mice were treated with BMS-303141, and blood glucose responses, hyperpolarized alanine labeling, and aminotransferase activity were evaluated. Western blotting was performed to assess ACLY phosphorylation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hyperpolarized alanine labeling was markedly elevated in db\/db livers, reflecting enhanced transamination capacity. Pharmacologic ACLY inhibition attenuated alanine- and glutamine-induced hyperglycemia and normalized alanine labeling within 2\u20134 h, without altering aminotransferase gene expression. These in vivo changes correlated with increased hepatic ACLY phosphorylation and ex vivo ALT assay results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Together, these findings support a model in which ACLY facilitates amino acid\u2013driven gluconeogenesis through metabolic control of ALT-mediated transamination, consistent with increased pyruvate\u2013alanine exchange. Hyperpolarized [1-\n                      <jats:sup>13<\/jats:sup>\n                      C]pyruvate MRS thereby provides a sensitive, translational readout of dynamic hepatic metabolism relevant to NAFLD and T2DM.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1663958","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T05:19:01Z","timestamp":1761542341000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["ACLY facilitates alanine flux in the livers of db\/db mice: a hyperpolarized [1-13C]pyruvate MRS study"],"prefix":"10.3389","volume":"16","author":[{"given":"Young-Suk","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae 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