title: The liver-enriched transcription factor CREBH is nutritionally regulated and activated by fatty acids and PPARalpha.
abstract: To elucidate the physiological role of CREBH, the hepatic mRNA and protein levels of CREBH were estimated in various feeding states of wild and obesity mice. In the fast state, the expression of CREBH mRNA and nuclear protein were high and profoundly suppressed by refeeding in the wild-type mice. In ob/ob mice, the refeeding suppression was impaired. The diet studies suggested that CREBH expression was activated by fatty acids. CREBH mRNA levels in the mouse primary hepatocytes were elevated by addition of the palmitate, oleate and eicosapenonate. It was also induced by PPARalpha agonist and repressed by PPARalpha antagonist. Luciferase reporter gene assays indicated that the CREBH promoter activity was induced by fatty acids and co-expression of PPARalpha. Deletion studies identified the PPRE for PPARalpha activation. Electrophoretic mobility shift assay and chromatin immunoprecipitation (ChIP) assay confirmed that PPARalpha directly binds to the PPRE. Activation of CREBH at fasting through fatty acids and PPARalpha suggest that CREBH is involved in nutritional regulation.
authors.affiliation: Department of Internal Medicine (Endocrinology and Metabolism), Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba Ibaraki 305-8575, Japan.
authors.forename: Hirosuke
authors.initials: H
authors.lastname: Danno
authors.forename: Kiyo-aki
authors.initials: KA
authors.lastname: Ishii
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Motoki
authors.initials: M
authors.lastname: Mikami
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yabe
authors.forename: Mika
authors.initials: M
authors.lastname: Furusawa
authors.forename: Shin
authors.initials: S
authors.lastname: Kumadaki
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Watanabe
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Shimizu
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuzaka
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Takahashi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yatoh
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Yamada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimano
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005215:Fasting; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
chemical_list: C500051:Creb3l3 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D005227:Fatty Acids; D047493:PPAR alpha