In vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression

Journal Article · Fri Nov 16 04:00:00 EST 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.08.165· OSTI ID:21032974

Takeuchi, Yoshinori ^[1]; Yahagi, Naoya ^[1]; Nakagawa, Yoshimi; Matsuzaka, Takashi ^[2]; Shimizu, Ritsuko ^[3]; Sekiya, Motohiro; Iizuka, Yoko; Ohashi, Ken; Gotoda, Takanari ^[1]; Yamamoto, Masayuki ^[3]; Nagai, Ryozo; Kadowaki, Takashi ^[1]; Yamada, Nobuhiro ^[2]; Osuga, Jun-ichi ^[1]; Shimano, Hitoshi ^[2]

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1. Department of Internal Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655 (Japan)
2. Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 (Japan)
3. Center for Tsukuba Advance Research Alliance, University of Tsukuba, Ibaraki 305-8575 (Japan)

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 2.2 kb 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 2.2 kb 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.

• OSTI ID: 21032974
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 363; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADENOVIRUS
ADIPOSE TISSUE
GENE REGULATION
IN VIVO
INSULIN
LIVER
LUCIFERASE
PROMOTERS
STEROLS
STREPTOZOCIN
TRANSCRIPTION
TRANSGENIC MICE