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However, the role of TET1 in metabolic homeostasis keeps unknown. Here, our finding demonstrates that hepatic TET1 physically interacts with silent information regulator T1 (SIRT1)\n                    <jats:italic>via<\/jats:italic>\n                    its C-terminal and activates its deacetylase activity, further regulating the acetylation-dependent cellular translocalization of transcriptional factors PGC-1\u03b1 and FOXO1, resulting in the activation of hepatic gluconeogenic gene expression that includes\n                    <jats:italic>PPARGC1A<\/jats:italic>\n                    ,\n                    <jats:italic>G6PC<\/jats:italic>\n                    , and\n                    <jats:italic>SLC2A4<\/jats:italic>\n                    . Importantly, the hepatic gluconeogenic gene activation program induced by fasting is inhibited in\n                    <jats:italic>Tet1<\/jats:italic>\n                    heterozygous mice livers. The adenosine 5\u2019-monophosphate-activated protein kinase (AMPK) activators metformin or AICAR\u2014two compounds that mimic fasting\u2014elevate hepatic gluconeogenic gene expression dependent on in turn activation of the AMPK-TET1-SIRT1 axis. Collectively, our study identifies TET1 as a SIRT1 coactivator and demonstrates that the AMPK-TET1-SIRT1 axis represents a potential mechanism or therapeutic target for glucose metabolism or metabolic diseases.\n                  <\/jats:p>","DOI":"10.7554\/elife.70672","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T09:00:26Z","timestamp":1636102826000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.70672","source":"Crossref","is-referenced-by-count":32,"title":["The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9618-9415","authenticated-orcid":true,"given":"Chunbo","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University","place":["Ganzhou, China"]},{"name":"School of Pharmacy, Nanchang 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