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

Yoshinori Takeuchi, Naoya Yahagi, Yoshimi Nakagawa, Takashi Matsuzaka, Ritsuko Shimizu, Motohiro Sekiya, Yoko Iizuka, Ken Ohashi, Takanari Gotoda, Masayuki Yamamoto, Ryozo Nagai, Takashi Kadowaki, Nobuhiro Yamada, Jun ichi Osuga, Hitoshi Shimano

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 2.2 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.

Original languageEnglish
Pages (from-to)329-335
Number of pages7
JournalBiochemical and biophysical research communications
Volume363
Issue number2
DOIs
Publication statusPublished - 2007 Nov 16
Externally publishedYes

Keywords

  • Adenovirus
  • Adipose tissue
  • Insulin
  • Lipogenesis
  • Liver
  • Promoter analysis
  • Transcription
  • Transgenic mouse

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Takeuchi, Y., Yahagi, N., Nakagawa, Y., Matsuzaka, T., Shimizu, R., Sekiya, M., Iizuka, Y., Ohashi, K., Gotoda, T., Yamamoto, M., Nagai, R., Kadowaki, T., Yamada, N., Osuga, J. I., & Shimano, H. (2007). In vivo promoter analysis on refeeding response of hepatic sterol regulatory element-binding protein-1c expression. Biochemical and biophysical research communications, 363(2), 329-335. https://doi.org/10.1016/j.bbrc.2007.08.165