Version 1
: Received: 10 February 2021 / Approved: 11 February 2021 / Online: 11 February 2021 (10:36:17 CET)
How to cite:
Pantha, R.; Lee, J.; Bae, J.; Koh, E.H.; Song, D.; Im, S. LRH-1 Ameliorates Hepatic Triglyceride Accumulation via Regulation of Perilipin 5 in the Liver. Preprints2021, 2021020276 (doi: 10.20944/preprints202102.0276.v1).
Pantha, R.; Lee, J.; Bae, J.; Koh, E.H.; Song, D.; Im, S. LRH-1 Ameliorates Hepatic Triglyceride Accumulation via Regulation of Perilipin 5 in the Liver. Preprints 2021, 2021020276 (doi: 10.20944/preprints202102.0276.v1).
Cite as:
Pantha, R.; Lee, J.; Bae, J.; Koh, E.H.; Song, D.; Im, S. LRH-1 Ameliorates Hepatic Triglyceride Accumulation via Regulation of Perilipin 5 in the Liver. Preprints2021, 2021020276 (doi: 10.20944/preprints202102.0276.v1).
Pantha, R.; Lee, J.; Bae, J.; Koh, E.H.; Song, D.; Im, S. LRH-1 Ameliorates Hepatic Triglyceride Accumulation via Regulation of Perilipin 5 in the Liver. Preprints 2021, 2021020276 (doi: 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.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
