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.
Rubee Pantha