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As AMPK has a wide range of protein and gene targets, defining its role has been difficult. Here, we have studied a transgenic mouse model overexpressing the constitutively active \u03b11 subunit of <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> in endothelial cells (<jats:styled-content style=\"fixed-case\">EC\u2010AMPK<\/jats:styled-content>) to elucidate its role in energy homeostasis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Wild\u2010type and <jats:styled-content style=\"fixed-case\">EC\u2010AMPK<\/jats:styled-content> mice were fed with a high fat diet for 16 weeks. Drugs (or vehicles) were given daily by oral gavage. Body weight, fat mass composition, glucose and lipid levels were monitored regularly. Tissues including aortae and liver were collected for quantitative <jats:styled-content style=\"fixed-case\">RT\u2010PCR<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>estern blotting, <jats:sc>elisa<\/jats:sc>, histological and biochemical evaluations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Compared with wild\u2010type animals, high fat diet caused more severe metabolic defects in <jats:styled-content style=\"fixed-case\">EC\u2010AMPK<\/jats:styled-content> mice, which exhibited increased body weight and fat mass, elevated blood pressure, augmented glucose and lipid levels, impaired glucose tolerance, hepatomegaly and steatohepatitis. Constitutive activation of <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> \u03b11 in endothelial cells induced <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102 expression and arterial inflammation. Genes involved in lipid metabolism were down\u2010regulated in aortae and livers of <jats:styled-content style=\"fixed-case\">EC\u2010AMPK<\/jats:styled-content> mice. Chronic treatment with selective <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102 inhibitors, celecoxib or nimesulide, significantly ameliorated arterial inflammation, steatohepatitis and hyperlipidaemia in <jats:styled-content style=\"fixed-case\">EC\u2010AMPK<\/jats:styled-content> mice, without altering their blood pressure or clotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Constitutive activation of endothelial <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content> \u03b11 promotes vascular inflammation and the development of obesity\u2010induced fatty livers largely via induction of <jats:styled-content style=\"fixed-case\">COX<\/jats:styled-content>\u20102.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12482","type":"journal-article","created":{"date-parts":[[2013,10,25]],"date-time":"2013-10-25T17:15:31Z","timestamp":1382721331000},"page":"498-508","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Constitutive activation of <scp>AMPK<\/scp> \u03b11 in vascular endothelium promotes high\u2010fat diet\u2010induced fatty liver injury: role of <scp>COX<\/scp>\u20102 induction"],"prefix":"10.1111","volume":"171","author":[{"given":"Yan","family":"Liang","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacy LKS Faculty of Medicine The University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bosheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacy LKS Faculty of Medicine The University of 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