{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360004233979251968.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1074/jbc.m112.384545"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0021925820621871?httpAccept=text/xml"}},{"identifier":{"@type":"URI","@value":"https://api.elsevier.com/content/article/PII:S0021925820621871?httpAccept=text/plain"}},{"identifier":{"@type":"URI","@value":"https://syndication.highwire.org/content/doi/10.1074/jbc.M112.384545"}},{"identifier":{"@type":"PMID","@value":"23024365"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Leptin Activates Hepatic 5′-AMP-activated Protein Kinase through Sympathetic Nervous System and α1-Adrenergic Receptor"}],"description":[{"notation":[{"@value":"AMPK activation promotes glucose and lipid metabolism.Hepatic AMPK activities were decreased in fatty liver from lipodystrophic mice, and leptin activated the hepatic AMPK via the α-adrenergic effect.Leptin improved the fatty liver possibly by activating hepatic AMPK through the central and sympathetic nervous systems.Hepatic AMPK plays significant roles in the pathophysiology of lipodystrophy and metabolic action of leptin. Leptin is an adipocyte-derived hormone that regulates energy homeostasis. Leptin treatment strikingly ameliorates metabolic disorders of lipodystrophy, which exhibits ectopic fat accumulation and severe insulin-resistant diabetes due to a paucity of adipose tissue. Although leptin is shown to activate 5'-AMP-activated protein kinase (AMPK) in the skeletal muscle, the effect of leptin in the liver is still unclear. We investigated the effect of leptin on hepatic AMPK and its pathophysiological relevance in A-ZIP/F-1 mice, a model of generalized lipodystrophy. Here, we demonstrated that leptin activates hepatic AMPK through the central nervous system and α-adrenergic sympathetic nerves. AMPK activities were decreased in the fatty liver of A-ZIP/F-1 mice, and leptin administration increased AMPK activities in the liver as well as in skeletal muscle with significant reduction in triglyceride content. Activation of hepatic AMPK with A769662 also led to a decrease in hepatic triglyceride content and blood glucose levels in A-ZIP/F-1 mice. These results indicate that the down-regulation of hepatic AMPK activities plays a pathophysiological role in the metabolic disturbances of lipodystrophy, and the hepatic AMPK activation is involved in the therapeutic effects of leptin."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004233979251980","@type":"Researcher","foaf:name":[{"@value":"Licht 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Nakao"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00219258"}],"prism:publicationName":[{"@value":"Journal of Biological Chemistry"}],"dc:publisher":[{"@value":"Elsevier BV"}],"prism:publicationDate":"2012-11","prism:volume":"287","prism:number":"48","prism:startingPage":"40441","prism:endingPage":"40447"},"reviewed":"false","dc:rights":["https://www.elsevier.com/tdm/userlicense/1.0/","http://creativecommons.org/licenses/by/4.0/"],"url":[{"@id":"https://api.elsevier.com/content/article/PII:S0021925820621871?httpAccept=text/xml"},{"@id":"https://api.elsevier.com/content/article/PII:S0021925820621871?httpAccept=text/plain"},{"@id":"https://syndication.highwire.org/content/doi/10.1074/jbc.M112.384545"}],"createdAt":"2012-10-01","modifiedAt":"2022-01-05","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Leptin","dc:title":"Leptin"},{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Sympathetic%20Nervous%20System","dc:title":"Sympathetic Nervous System"},{"@id":"https://cir.nii.ac.jp/all?q=Lipodystrophy","dc:title":"Lipodystrophy"},{"@id":"https://cir.nii.ac.jp/all?q=AMP-Activated%20Protein%20Kinases","dc:title":"AMP-Activated Protein Kinases"},{"@id":"https://cir.nii.ac.jp/all?q=Rats","dc:title":"Rats"},{"@id":"https://cir.nii.ac.jp/all?q=Fatty%20Liver","dc:title":"Fatty Liver"},{"@id":"https://cir.nii.ac.jp/all?q=Mice,%20Inbred%20C57BL","dc:title":"Mice, Inbred C57BL"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Receptors,%20Adrenergic,%20alpha-1","dc:title":"Receptors, Adrenergic, alpha-1"},{"@id":"https://cir.nii.ac.jp/all?q=Hepatocytes","dc:title":"Hepatocytes"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=Female","dc:title":"Female"},{"@id":"https://cir.nii.ac.jp/all?q=Rats,%20Wistar","dc:title":"Rats, Wistar"},{"@id":"https://cir.nii.ac.jp/all?q=Muscle,%20Skeletal","dc:title":"Muscle, Skeletal"},{"@id":"https://cir.nii.ac.jp/all?q=Cells,%20Cultured","dc:title":"Cells, Cultured"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040000782064501504","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"21229013"},{"@type":"JGN","@value":"JP21229013"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21229013/"}],"notation":[{"@language":"ja","@value":"間葉系細胞由来ホルモンの生理作用とその破綻"},{"@language":"en","@value":"Physiological Function of Hormones Derived from Mesenchymal Cells and Its Failure"}]},{"@id":"https://cir.nii.ac.jp/crid/1040000782102809216","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"22126012"},{"@type":"JGN","@value":"JP22126012"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PLANNED-22126012/"}],"notation":[{"@language":"ja","@value":"脂肪蓄積による臓器機能破綻の分子基盤の解明"},{"@language":"en","@value":"Molecular Basis and 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