Sterol-mediated Regulation of Human Lipin 1 Gene Expression in Hepatoblastoma Cells

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2009 Jun 26

PMID 19553673

Citations 39

Authors

Kenji Ishimoto

Hiroki Nakamura

Keisuke Tachibana

Daisuke Yamasaki

Akemi Ota

Ken-Ichi Hirano

Toshiya Tanaka

Takao Hamakubo

Juro Sakai

Tatsuhiko Kodama

Takefumi Doi

Affiliations

Soon will be listed here.

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.

Citing Articles

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A diet high in glucose and deficient in dietary fibre causes fat accumulation in the liver without weight gain.

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Regulation and targeting of SREBP-1 in hepatocellular carcinoma.

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