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

J Biol Chem. 2009 Aug 14;284(33):22195-205. doi: 10.1074/jbc.M109.028753. Epub 2009 Jun 24.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • CCAAT-Binding Factor / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Hepatoblastoma / metabolism*
  • Humans
  • Liver Neoplasms / metabolism*
  • Molecular Sequence Data
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics*
  • Phosphatidate Phosphatase
  • Promoter Regions, Genetic
  • RNA, Small Interfering / metabolism
  • Response Elements
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Sterols / metabolism*
  • Transcription, Genetic
  • Triglycerides / metabolism

Substances

  • CCAAT-Binding Factor
  • Nuclear Proteins
  • RNA, Small Interfering
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Sterols
  • Triglycerides
  • nuclear factor Y
  • LPIN1 protein, human
  • Phosphatidate Phosphatase