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Here, we activated mediobasal hypothalamus (MBH) JAZF1 in high\u2010fat diet (HFD)\u2010fed rats by an adenovirus expressing JAZF1 (Ad\u2010\n                    <jats:italic>JAZF1<\/jats:italic>\n                    ). We evaluated the changes in the hypothalamic insulin receptor (InsR)\u2010PI3K\u2010Akt\u2010AMPK pathway and hepatic glucose production (HGP). To investigate the impact of MBH Ad\u2010\n                    <jats:italic>JAZF1<\/jats:italic>\n                    on HGP, we activated MBH JAZF1 in the presence or absence of ATP\u2010dependent potassium (K\n                    <jats:sub>ATP<\/jats:sub>\n                    ) channel inhibition, hepatic branch vagotomy (HVG), or an AMPK activator (AICAR). In HFD\u2010fed rats, MBH Ad\u2010\n                    <jats:italic>JAZF1<\/jats:italic>\n                    decreased body weight and food intake, and inhibited HGP by increasing hepatic insulin signaling. Under insulin stimulation, MBH Ad\u2010\n                    <jats:italic>JAZF1<\/jats:italic>\n                    increased InsR and Akt phosphorylation, and phosphatidylinositol 3, 4, 5\u2010trisphosphate (PIP3) formation; however, AMPK phosphorylation was decreased in the hypothalamus. The positive effect of MBH JAZF1 on hepatic insulin signaling and HGP was prevented by treatment with a K\n                    <jats:sub>ATP<\/jats:sub>\n                    channel inhibitor or HVG. The metabolic impact of hypothalamic JAZF1 was also blocked by MBH AICAR. Ad\u2010\n                    <jats:italic>JAZF1<\/jats:italic>\n                    treatment in SH\u2010SY5Y cells resulted in an elevation of InsR and Akt phosphorylation following insulin stimulation. Our findings show that hypothalamic JAZF1 regulates HGP\n                    <jats:italic>via<\/jats:italic>\n                    the InsR\u2010PI3K\u2010Akt\u2010AMPK pathway and K\n                    <jats:sub>ATP<\/jats:sub>\n                    channels.\n                  <\/jats:p>","DOI":"10.1096\/fj.201901836rr","type":"journal-article","created":{"date-parts":[[2020,4,10]],"date-time":"2020-04-10T09:15:47Z","timestamp":1586510147000},"page":"7058-7074","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Effect of central JAZF1 on glucose production is regulated by the PI3K\u2010Akt\u2010AMPK pathway"],"prefix":"10.1096","volume":"34","author":[{"given":"Mengjiao","family":"Zhou","sequence":"first","affiliation":[{"name":"The Key Laboratory of Laboratory Medical Diagnostics in the Ministry of Education Department of Clinical Biochemistry College of Laboratory Medicine Chongqing Medical University Chongqing 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