PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytes
Peroxisome proliferator-activator receptor (PPAR) γ is a nuclear hormone receptor that regulates glucose homeostasis, lipid metabolism, and adipocyte function. It has been shown that activation of PPARγ can reduce the incidence of gallstone. Herein we aimed to clarify the role of PPARγ in the reduct...
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doaj-22d755e18f474ac9a7f08d1cd4883a5e2020-11-25T00:35:52ZengElsevierJournal of Pharmacological Sciences1347-86132019-01-01139118PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytesTao Han0Yangge Lv1Shijia Wang2Tao Hu3Hao Hong4Zan Fu5Department of Intensive Care Unit, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, ChinaDepartment of Pharmacology, China Pharmaceutical University, Nanjing, 210009, Jiangsu, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, ChinaDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, ChinaDepartment of Pharmacology, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China; Corresponding author.Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China; Corresponding author.Peroxisome proliferator-activator receptor (PPAR) γ is a nuclear hormone receptor that regulates glucose homeostasis, lipid metabolism, and adipocyte function. It has been shown that activation of PPARγ can reduce the incidence of gallstone. Herein we aimed to clarify the role of PPARγ in the reduction of gallstones. The plasmid containing the coding sequence of PPARγ was constructed and transfected in the human liver cell line (L02 cells). Western blot and RT-PCR were used to detect hydroxyl-methyl-glutaryl-CoA reductase (HMGCR), sterol regulatory element-binding proteins 2 (SREBP2), 7α-hydroxylase (CYP7A1), adenosine triphosphate-binding cassette (ABC) sterol transporters G5 and G8 (ABCG5, ABCG8) and liver X receptor α (LXRα). The Amplex Red cholesterol assay kit was used to detect the intracellular or extracellular cholesterol level. Our data showed that PPARγ overexpression caused significant decreases in both extracellular and intracellular cholesterol in the L02 cells. The further studies indicated PPARγ overexpression substantially decreased expression of HMGCR and SREBP-2, increased expression of CYP7A1, ABCG5, ABCG8 and LXRα. These results indicated that upregulation of PPARγ may reduce cholesterol levels through multiple-pathways including HMGCR/SREBP2-mediated biosynthesis, CYP7A1-mediated transformation, and ABCG5/ABCG8-mediated efflux. We thus suggest that PPARγ might have beneficial effects for cholesterol gallstones diseases. Keywords: PPARγ, Cholesterol, HMGCR, CYP7A1 and ABCG5/8http://www.sciencedirect.com/science/article/pii/S134786131830210X |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tao Han Yangge Lv Shijia Wang Tao Hu Hao Hong Zan Fu |
spellingShingle |
Tao Han Yangge Lv Shijia Wang Tao Hu Hao Hong Zan Fu PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytes Journal of Pharmacological Sciences |
author_facet |
Tao Han Yangge Lv Shijia Wang Tao Hu Hao Hong Zan Fu |
author_sort |
Tao Han |
title |
PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytes |
title_short |
PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytes |
title_full |
PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytes |
title_fullStr |
PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytes |
title_full_unstemmed |
PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytes |
title_sort |
pparγ overexpression regulates cholesterol metabolism in human l02 hepatocytes |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2019-01-01 |
description |
Peroxisome proliferator-activator receptor (PPAR) γ is a nuclear hormone receptor that regulates glucose homeostasis, lipid metabolism, and adipocyte function. It has been shown that activation of PPARγ can reduce the incidence of gallstone. Herein we aimed to clarify the role of PPARγ in the reduction of gallstones. The plasmid containing the coding sequence of PPARγ was constructed and transfected in the human liver cell line (L02 cells). Western blot and RT-PCR were used to detect hydroxyl-methyl-glutaryl-CoA reductase (HMGCR), sterol regulatory element-binding proteins 2 (SREBP2), 7α-hydroxylase (CYP7A1), adenosine triphosphate-binding cassette (ABC) sterol transporters G5 and G8 (ABCG5, ABCG8) and liver X receptor α (LXRα). The Amplex Red cholesterol assay kit was used to detect the intracellular or extracellular cholesterol level. Our data showed that PPARγ overexpression caused significant decreases in both extracellular and intracellular cholesterol in the L02 cells. The further studies indicated PPARγ overexpression substantially decreased expression of HMGCR and SREBP-2, increased expression of CYP7A1, ABCG5, ABCG8 and LXRα. These results indicated that upregulation of PPARγ may reduce cholesterol levels through multiple-pathways including HMGCR/SREBP2-mediated biosynthesis, CYP7A1-mediated transformation, and ABCG5/ABCG8-mediated efflux. We thus suggest that PPARγ might have beneficial effects for cholesterol gallstones diseases. Keywords: PPARγ, Cholesterol, HMGCR, CYP7A1 and ABCG5/8 |
url |
http://www.sciencedirect.com/science/article/pii/S134786131830210X |
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