title: In vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression.
abstract: Sterol regulatory element-binding protein (SREBP)-1c is the master regulator of lipogenic gene expression in liver. The mRNA abundance of SREBP-1c is markedly induced when animals are refed after starvation, although the regulatory mechanism is so far unknown. To investigate the mechanism of refeeding response of SREBP-1c gene expression in vivo, we generated a transgenic mouse model that carries 2.2kb promoter region fused to the luciferase reporter gene. These transgenic mice exhibited refeeding responses of the reporter in liver and adipose tissues with extents essentially identical to those of endogenous SREBP-1c mRNA. The same results were obtained from experiments using adenovirus-mediated SREBP-1c-promoter-luciferase fusion gene transduction to liver. These data demonstrate that the regulation of SREBP-1c gene expression is at the transcription level, and that the 2.2kb 5'-flanking region is sufficient for this regulation. Moreover, when these transgenic or adenovirus-infected mice were placed on insulin-depleted state by streptozotocin treatment, the reporter expression was upregulated as strongly as in control mice, demonstrating that this regulation is not dominated by serum insulin level. These mice are the first models to provide the mechanistic insight into the transcriptional regulation of SREBP-1c gene in vivo.
authors: Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors: Yoshinori
authors: Y
authors: Takeuchi
authors: Naoya
authors: N
authors: Yahagi
authors: Yoshimi
authors: Y
authors: Nakagawa
authors: Takashi
authors: T
authors: Matsuzaka
authors: Ritsuko
authors: R
authors: Shimizu
authors: Motohiro
authors: M
authors: Sekiya
authors: Yoko
authors: Y
authors: Iizuka
authors: Ken
authors: K
authors: Ohashi
authors: Takanari
authors: T
authors: Gotoda
authors: Masayuki
authors: M
authors: Yamamoto
authors: Ryozo
authors: R
authors: Nagai
authors: Takashi
authors: T
authors: Kadowaki
authors: Nobuhiro
authors: N
authors: Yamada
authors: Jun-Ichi
authors: J
authors: Osuga
authors: Hitoshi
authors: H
authors: Shimano
mesh_terms: D000818:Animals; D005215:Fasting / Q000378:metabolism*; D005247:Feeding Behavior / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D051780:Sterol Regulatory Element Binding Protein 1