Sterol-mediated regulation of human lipin 1 gene expression in hepatoblastoma cells

Kenji Ishimoto, Hiroki Nakamura, Keisuke Tachibana, Daisuke Yamasaki, Akemi Ota, Ken Ichi Hirano, Toshiya Tanaka, Takao Hamakubo, Juro Sakai, Tatsuhiko Kodama, Takefumi Doi

Research output: Contribution to journalArticlepeer-review

53 Citations (Scopus)

Abstract

Lipin 1 plays a crucial role in lipid metabolism in adipose tissue, skeletal muscle, and liver. Its physiological role involves two cellular functions: regulation of phosphatidate phosphatase activity and regulation of fatty acid oxidation. In this study, we have demonstrated that lipin 1 gene (LPIN1) expression is regulated by cellular sterols, which are key regulators of lipid metabolism. We have also characterized the sterol-response element and nuclear factor Y-binding sites in the human LPIN1 promoter. Using a luciferase assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, we demonstrated that these elements are responsible for the transcription of LPIN1 gene, mediated by SREBP-1 (sterol regulatory element-binding protein 1) and nuclear factor Y. Furthermore, we investigated whether lipin 1 is involved in lipogenesis by transfection of LPIN1 small interfering RNA. We infer that sterol-mediated regulation of lipin 1 gene transcription modulates triglyceride accumulation. This modulation involves changes in the activity of phosphatidate phosphatase.

Original languageEnglish
Pages (from-to)22195-22205
Number of pages11
JournalJournal of Biological Chemistry
Volume284
Issue number33
DOIs
Publication statusPublished - 2009 Aug 14

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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