Perilipin 5 is a novel target of nuclear receptor LRH-1 to regulate hepatic triglycerides metabolism
| Autor: | Seung Soon Im, Minsang Shin, Jae-Ho Lee, Eun Hee Koh, Rubee Pantha, Dae-Kyu Song, Jae-Hoon Bae |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Receptors Cytoplasmic and Nuclear Lipid droplet Biochemistry Perilipin-5 Article Mice Western blot Internal medicine medicine Animals Humans Receptor Promoter Regions Genetic Molecular Biology Triglycerides Mice Knockout Liver receptor homolog-1 Binding Sites medicine.diagnostic_test Bile acid Chemistry Lipid metabolism General Medicine Fasting Hep G2 Cells Lipid Droplets Endocrinology Nuclear receptor Liver Perilipin Hepatocytes Chromatin immunoprecipitation Perilipin 5 Protein Binding |
| Zdroj: | BMB Reports |
| ISSN: | 1976-670X 1976-6696 |
| Popis: | Liver receptor homolog-1 (LRH-1) has emerged as a regulator of hepatic glucose, bile acid, and mitochondrial metabolism. However, the functional mechanism underlying the effect of LRH-1 on lipid mobilization has not been addressed. This study investigated the regulatory function of LRH-1 in lipid metabolism in maintaining a normal liver physiological state during fasting. The Lrh-1f/f and LRH-1 liver-specific knockout (Lrh-1LKO) mice were either fed or fasted for 24 h, and the liver and serum were isolated. The livers were used for qPCR, western blot, and histological analysis. Primary hepatocytes were isolated for immunocytochemistry assessments of lipids. During fasting, the Lrh-1LKO mice showed increased accumulation of triglycerides in the liver compared to that in Lrh-1f/f mice. Interestingly, in the Lrh-1LKO liver, decreases in perilipin 5 (PLIN5) expression and genes involved in β-oxidation were observed. In addition, the LRH-1 agonist dialauroylphosphatidylcholine also enhanced PLIN5 expression in human cultured HepG2 cells. To identify new target genes of LRH-1, these findings directed us to analyze the Plin5 promoter sequence, which revealed -1620/-1614 to be a putative binding site for LRH-1. This was confirmed by promoter activity and chromatin immunoprecipitation assays. Additionally, fasted Lrh-1f/f primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted Lrh-1LKO primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs, protect the liver from lipid overload, and manage the cellular needs during fasting. [BMB Reports 2021; 54(9): 476-481]. |
| Databáze: | OpenAIRE |
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