title: ASK1 signalling regulates brown and beige adipocyte function.
abstract: Recent studies suggest that adult humans have active brown or beige adipocytes, the activation of which might be a therapeutic strategy for the treatment of diverse metabolic diseases. Here we show that the protein kinase ASK1 regulates brown and beige adipocytes function. In brown or white adipocytes, the PKA-ASK1-p38 axis is activated in response to cAMP signalling and contributes to the cell-autonomous induction of genes, including Ucp1. Global and fat-specific ASK1 deficiency leads to impaired metabolic responses, including thermogenesis and oxygen consumption, at the cell and whole-body levels, respectively. Our data thus indicate that the ASK1 signalling axis is a regulator of brown and beige adipocyte gene expression and function.
authors.affiliation: The laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hattori
authors.affiliation: The laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Naguro
authors.affiliation: The laboratory of Bioanalytical Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.|JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Kohki
authors.initials: K
authors.lastname: Okabe
authors.affiliation: The laboratory of Bioanalytical Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Funatsu
authors.affiliation: The laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Furutani
authors.affiliation: Division of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Takeda
authors.affiliation: The laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ichijo
mesh_terms: D041721:3T3-L1 Cells; D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism*; D052438:Adipocytes, White / Q000166:cytology / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption / Q000235:genetics; D015398:Signal Transduction; D022722:Thermogenesis / Q000235:genetics*; D000071256:Uncoupling Protein 1; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human