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

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 sterolmediated regulation of lipin 1 gene transcription modulates triglyceride accumulation. This modulation involves changes in the activity of phosphatidate phosphatase.

Estrogen-related Receptor γ (ERRγ) Is a Novel Transcriptional Regulator of Phosphatidic Acid Phosphatase, LIPIN1, and Inhibits Hepatic Insulin Signaling

“…It is known to be induced by glucocorticoids in adipose tissues and the liver and by ␤-adrenergic signaling in skeletal muscle through the glucocorticoid receptor and the orphan nuclear receptor NOR-1 (40,41). It has also been reported that LIPIN1 is a target of SREBP-1 (sterol regulatory element-binding protein 1) and nuclear factor Y in hepatoblastoma cells (42). While this study was being carried out, one report was published regarding the role of LIPIN1 in cardiac myocytes.…”

Hypoxia causes triglyceride accumulation via HIF-1-mediated stimulation of lipin 1 expression

“…HRE 1 is conserved (Fig. 7B) as it is perfectly matched by a potential distal HRE in the mouse Lpin1 promoter region and is found close to the only other known distal regulatory elements, the SRE and NF-Y sites (Ishimoto et al, 2009). Finally, mutation of HRE 1 (Fig.…”

PPAR control: it's SIRTainly as easy as PGC

“…Of interest, it has been reported recently that the lipogenic transcription factor SREBP-1 is involved in the regulation of lipin-1 expression (Fig. 3) and that lipin-1 protein is induced by sterol depletion (Ishimoto et al 2009). In addition, lipin-1 gene expression is induced by T0901317, an activating ligand for the LXR (Ishimoto et al 2009).…”

“…3) and that lipin-1 protein is induced by sterol depletion (Ishimoto et al 2009). In addition, lipin-1 gene expression is induced by T0901317, an activating ligand for the LXR (Ishimoto et al 2009).…”