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

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

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Graduate School of Pharmaceutical Sciences, Osaka University, Department of Molecular Pharmaceutical Science, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.


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.

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