title: Transcriptional regulation of an insulin-sensitizing adipokine adipolin/CTRP12 in adipocytes by Krüppel-like factor 15.
abstract: Obese states characterized by chronic inflammation are closely linked to the development of metabolic dysfunction. We identified adipolin/CTRP12 as an insulin-sensitizing and anti-inflammatory adipokine. Although obese conditions down-regulate adipolin expression, its molecular mechanism is largely unknown. Here we show that the transcriptional regulator Krüppel-like factor (KLF) 15 is involved in the regulation of adipolin expression in adipocytes. White adipose tissue from diet-induced obese (DIO) mice showed decreased expression of KLF9 and KLF15 among several KLFs, which was accompanied by reduced expression of adipolin. In cultured 3T3L1 adipocytes, treatment with TNFα significantly reduced the mRNA levels of KLF9, KLF15 and adipolin. Adenovirus-mediated overexpression of KLF15 but not KLF9 reversed TNFα-induced reduction of adipolin expression in adipocytes. Conversely, gene targeting ablation of KLF15 attenuated adipolin expression in adipocytes. Expression of KLF15 but not KLF9 enhanced the promoter activity of adipolin in HEK293 cells. Pretreatment of 3T3L1 adipocytes with the JNK inhibitor SP600125, but not p38 MAPK inhibitor SB203580 blocked the inhibitory effects of TNFα on adipolin and KLF15 expression. These data suggest that adipose inflammation under conditions of obesity suppresses adipolin expression via JNK-dependent down-regulation of KLF15 in adipocytes.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Enomoto
authors.affiliation: Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kambara
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Uemura
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yuasa
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kataoka
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Miyabe
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Joki
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Hayakawa
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Hiramatsu-Ito
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.affiliation: Department of Molecular Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D054392:Adipokines / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D054392:Adipokines; C568466:C1qtnf12 protein, mouse; D004268:DNA-Binding Proteins; C467418:Klf15 protein, mouse; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha