Pantha, R.; Lee, J.-H.; Bae, J.-H.; Koh, E. H.; Song, D.-K.; Im, S.-S. LRH-1 Ameliorates Hepatic Triglyceride Accumulation via Regulation of Perilipin 5 in the Liver. Preprints2021, 2021020276. https://doi.org/10.20944/preprints202102.0276.v1
APA Style
Pantha, R., Lee, J. H., Bae, J. H., Koh, E. H., Song, D. K., & Im, S. S. (2021). LRH-1 Ameliorates Hepatic Triglyceride Accumulation via Regulation of Perilipin 5 in the Liver. Preprints. https://doi.org/10.20944/preprints202102.0276.v1
Chicago/Turabian Style
Pantha, R., Dae-Kyu Song and Seung-Soon Im. 2021 "LRH-1 Ameliorates Hepatic Triglyceride Accumulation via Regulation of Perilipin 5 in the Liver" Preprints. https://doi.org/10.20944/preprints202102.0276.v1
Abstract
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 during fasting. The wild-type (WT) and LRH-1 liver-specific knockout (LKO) mice were either fed or fasted for 24 h, and the liver and serum were isolated. During fasting, the LRH-1 LKO mice showed greater accumulation of triglycerides in the liver compared to that in WT mice. Interestingly, LRH-1 LKO liver decreased the perilipin 5 (PLIN5) expression and genes involved in β-oxidation. Additionally, 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 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 immuno-precipitation assays. Moreover, fasted WT primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted LRH-1 LKO primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs and manage the cellular needs.
Biology and Life Sciences, Biochemistry and Molecular Biology
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