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Subsequently, m\n                    <jats:sup>6<\/jats:sup>\n                    A readers bind to m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010marked RNA to influence its metabolism. RNA m\n                    <jats:sup>6<\/jats:sup>\n                    A emerges to critically regulate multiple intracellular processes; however, there is a gap in our understanding of m\n                    <jats:sup>6<\/jats:sup>\n                    A in liver metabolism. Glucose\u20106\u2010phosphatase catalytic subunit (G6pc) mediates hepatic glucose production (HGP) and serves as the gatekeeper for glycogenolysis and gluconeogenesis; however, G6pc regulation is not fully understood. Here, METTL14 is identified as a posttranscriptional regulator of G6pc. Liver METTL14, METTL3, and m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010methylated\n                    <jats:italic>G6pc<\/jats:italic>\n                    mRNA are upregulated in mice with diet\u2010induced obesity. Deletion of\n                    <jats:italic>Mettl14<\/jats:italic>\n                    decreases, whereas overexpression of METTL14 increases,\n                    <jats:italic>G6pc<\/jats:italic>\n                    mRNA m\n                    <jats:sup>6<\/jats:sup>\n                    A in hepatocytes in vitro and in vivo. Five m\n                    <jats:sup>6<\/jats:sup>\n                    A sites are identified, and disruption of them (\n                    <jats:italic>G6pc<\/jats:italic>\n                    <jats:sup>\u0394<\/jats:sup>\n                    <jats:italic>\n                      <jats:sup>5A<\/jats:sup>\n                    <\/jats:italic>\n                    ) blocks METTL14\u2010induced m\n                    <jats:sup>6<\/jats:sup>\n                    A methylation of\n                    <jats:italic>G6pc<\/jats:italic>\n                    <jats:sup>\u0394<\/jats:sup>\n                    <jats:italic>\n                      <jats:sup>5A<\/jats:sup>\n                    <\/jats:italic>\n                    mRNA. METTL14 increases both stability and translation of\n                    <jats:italic>G6pc<\/jats:italic>\n                    but not\n                    <jats:italic>G6pc<\/jats:italic>\n                    <jats:sup>\u0394<\/jats:sup>\n                    <jats:italic>\n                      <jats:sup>5A<\/jats:sup>\n                    <\/jats:italic>\n                    mRNA. YTHDF1 and YTHDF3 but not YTHDF2 (m\n                    <jats:sup>6<\/jats:sup>\n                    A readers) bind to m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010marked\n                    <jats:italic>G6pc<\/jats:italic>\n                    mRNA to increase its synthesis. Deletion of hepatic\n                    <jats:italic>Mettl14<\/jats:italic>\n                    decreases gluconeogenesis in primary hepatocytes, liver slices, and mice. Hepatocyte\u2010specific restoration of G6pc reverses defective HGP in\n                    <jats:italic>Mettl14<\/jats:italic>\n                    knockout mice. These results unveil a METTL14\/\n                    <jats:italic>G6pc<\/jats:italic>\n                    mRNA m\n                    <jats:sup>6<\/jats:sup>\n                    A\/G6pc biosynthesis\/HGP axis governing glucose metabolism in health and metabolic disease.\n                  <\/jats:p>","DOI":"10.1002\/advs.202417355","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T10:34:50Z","timestamp":1745577290000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["METTL14\u2010Induced M\n                    <sup>6<\/sup>\n                    A Methylation Increases G6pc Biosynthesis, Hepatic Glucose Production and Metabolic Disorders in Obesity"],"prefix":"10.1002","volume":"12","author":[{"given":"Qiantao","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Molecular and Integrative Physiology University of Michigan Medical School  Ann Arbor MI 48109 USA"},{"name":"Elizabeth Weiser Caswell Diabetes Institute University of Michigan  Michigan 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology University of Michigan Medical School  Ann Arbor MI 48109 USA"},{"name":"Department of Infectious Diseases Hunan Key Laboratory of Viral Hepatitis Xiangya Hospital Central South University  Changsha 410008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology University of Michigan Medical School  Ann Arbor MI 48109 USA"},{"name":"Elizabeth Weiser Caswell Diabetes Institute University of Michigan  Michigan 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology University of Michigan Medical School  Ann Arbor MI 48109 USA"},{"name":"Elizabeth Weiser Caswell Diabetes Institute University of Michigan  Michigan 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Decheng","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Chicago  Chicago IL 60637 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Life Sciences Wuhan University  Wuhan 430072 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8433-8137","authenticated-orcid":false,"given":"Liangyou","family":"Rui","sequence":"additional","affiliation":[{"name":"Department of Molecular and Integrative Physiology University of Michigan Medical School  Ann Arbor MI 48109 USA"},{"name":"Elizabeth Weiser Caswell Diabetes Institute University of 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