The liver-enriched transcription factor CREBH is nutritionally regulated and activated by fatty acids and PPARalpha.
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.
Danno
Hirosuke
H
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.
Ishii
Kiyo-aki
KA
Nakagawa
Yoshimi
Y
Mikami
Motoki
M
Yamamoto
Takashi
T
Yabe
Sachiko
S
Furusawa
Mika
M
Kumadaki
Shin
S
Watanabe
Kazuhisa
K
Shimizu
Hidehisa
H
Matsuzaka
Takashi
T
Kobayashi
Kazuto
K
Takahashi
Akimitsu
A
Yatoh
Shigeru
S
Suzuki
Hiroaki
H
Yamada
Nobuhiro
N
Shimano
Hitoshi
H
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
C500051:Creb3l3 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D005227:Fatty Acids; D047493:PPAR alpha