Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXRα) and Pregnane X Receptor (PXR)
Liver X receptor (LXR) is a nuclear receptor that regulates various biological processes, including de novo lipogenesis, cholesterol metabolism, and inflammation. Selective inhibition of LXR may aid the treatment of nonalcoholic fatty liver disease (NAFLD). Sesamin is a naturally occurring lignan in...
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doaj-d9aba9b562de47b1a74c41d76e53be672020-11-25T01:44:11ZengHindawi LimitedEvidence-Based Complementary and Alternative Medicine1741-427X1741-42882019-01-01201910.1155/2019/94016489401648Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXRα) and Pregnane X Receptor (PXR)Tsai-Sung Tai0Ni Tien1Hsin-Yi Shen2Fang-Yi Chu3Charles C. N. Wang4Chieh-Hsiang Lu5Hui-I Yu6Fang-Ping Kung7Hsiang-Hsun Chuang8Ying-Ray Lee9Hsiao-Yun Chang10Yun-Ping Lim11Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60080, Taiwan, ChinaDepartment of Laboratory Medicine, China Medical University Hospital, Taichung 40458, Taiwan, ChinaDepartment of Pharmacy, College of Pharmacy, China Medical University, Taichung 40458, Taiwan, ChinaDepartment of Pharmacy, College of Pharmacy, China Medical University, Taichung 40458, Taiwan, ChinaDepartment of Bioinformatics and Medical Engineering, Asia University, Taichung 40458, Taiwan, ChinaDepartment of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60080, Taiwan, ChinaDepartment of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60080, Taiwan, ChinaDepartment of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60080, Taiwan, ChinaDepartment of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60080, Taiwan, ChinaDepartment of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60080, Taiwan, ChinaDepartment of Biotechnology, Asia University, Taichung 40458, Taiwan, ChinaDepartment of Pharmacy, College of Pharmacy, China Medical University, Taichung 40458, Taiwan, ChinaLiver X receptor (LXR) is a nuclear receptor that regulates various biological processes, including de novo lipogenesis, cholesterol metabolism, and inflammation. Selective inhibition of LXR may aid the treatment of nonalcoholic fatty liver disease (NAFLD). Sesamin is a naturally occurring lignan in many dietary plants and has a wide range of beneficial effects on metabolism. The mechanism underlying sesamin action especially on the regulation of LXR remains elusive. Reporter assays, mRNA and protein expression, and in silico modeling were used to identify sesamin as an antagonist of LXRα. Sesamin was applied to the hepatic HepaRG and intestinal LS174T cells and showed that it markedly ameliorated lipid accumulation in the HepaRG cells, by reducing LXRα transactivation, inhibiting the expression of downstream target genes. This effect was associated with the stimulation of AMP-activated protein kinase (AMPK) signaling pathway, followed by decreased T0901317-LXRα-induced expression of SREBP-1c and its downstream target genes. Mechanistically, sesamin reduced the recruitment of SRC-1 but enhanced that of SMILE to the SREBP-1c promoter region under T0901317 treatment. It regulated the transcriptional control exerted by LXRα by influencing its interaction with coregulators and thus decreased mRNA and protein levels of genes downstream of LXRα and reduced lipid accumulation in hepatic cells. Additionally, sesamin reduced valproate- and rifampin-induced LXRα and pregnane X receptor (PXR) transactivation. This was associated with reduced expression of target genes and decreased lipid accumulation. Thus, sesamin is an antagonist of LXRα and PXR and suggests that it may alleviate drug-induced lipogenesis via the suppression of LXRα and PXR signaling.http://dx.doi.org/10.1155/2019/9401648 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tsai-Sung Tai Ni Tien Hsin-Yi Shen Fang-Yi Chu Charles C. N. Wang Chieh-Hsiang Lu Hui-I Yu Fang-Ping Kung Hsiang-Hsun Chuang Ying-Ray Lee Hsiao-Yun Chang Yun-Ping Lim |
spellingShingle |
Tsai-Sung Tai Ni Tien Hsin-Yi Shen Fang-Yi Chu Charles C. N. Wang Chieh-Hsiang Lu Hui-I Yu Fang-Ping Kung Hsiang-Hsun Chuang Ying-Ray Lee Hsiao-Yun Chang Yun-Ping Lim Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXRα) and Pregnane X Receptor (PXR) Evidence-Based Complementary and Alternative Medicine |
author_facet |
Tsai-Sung Tai Ni Tien Hsin-Yi Shen Fang-Yi Chu Charles C. N. Wang Chieh-Hsiang Lu Hui-I Yu Fang-Ping Kung Hsiang-Hsun Chuang Ying-Ray Lee Hsiao-Yun Chang Yun-Ping Lim |
author_sort |
Tsai-Sung Tai |
title |
Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXRα) and Pregnane X Receptor (PXR) |
title_short |
Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXRα) and Pregnane X Receptor (PXR) |
title_full |
Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXRα) and Pregnane X Receptor (PXR) |
title_fullStr |
Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXRα) and Pregnane X Receptor (PXR) |
title_full_unstemmed |
Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXRα) and Pregnane X Receptor (PXR) |
title_sort |
sesamin, a naturally occurring lignan, inhibits ligand-induced lipogenesis through interaction with liver x receptor alpha (lxrα) and pregnane x receptor (pxr) |
publisher |
Hindawi Limited |
series |
Evidence-Based Complementary and Alternative Medicine |
issn |
1741-427X 1741-4288 |
publishDate |
2019-01-01 |
description |
Liver X receptor (LXR) is a nuclear receptor that regulates various biological processes, including de novo lipogenesis, cholesterol metabolism, and inflammation. Selective inhibition of LXR may aid the treatment of nonalcoholic fatty liver disease (NAFLD). Sesamin is a naturally occurring lignan in many dietary plants and has a wide range of beneficial effects on metabolism. The mechanism underlying sesamin action especially on the regulation of LXR remains elusive. Reporter assays, mRNA and protein expression, and in silico modeling were used to identify sesamin as an antagonist of LXRα. Sesamin was applied to the hepatic HepaRG and intestinal LS174T cells and showed that it markedly ameliorated lipid accumulation in the HepaRG cells, by reducing LXRα transactivation, inhibiting the expression of downstream target genes. This effect was associated with the stimulation of AMP-activated protein kinase (AMPK) signaling pathway, followed by decreased T0901317-LXRα-induced expression of SREBP-1c and its downstream target genes. Mechanistically, sesamin reduced the recruitment of SRC-1 but enhanced that of SMILE to the SREBP-1c promoter region under T0901317 treatment. It regulated the transcriptional control exerted by LXRα by influencing its interaction with coregulators and thus decreased mRNA and protein levels of genes downstream of LXRα and reduced lipid accumulation in hepatic cells. Additionally, sesamin reduced valproate- and rifampin-induced LXRα and pregnane X receptor (PXR) transactivation. This was associated with reduced expression of target genes and decreased lipid accumulation. Thus, sesamin is an antagonist of LXRα and PXR and suggests that it may alleviate drug-induced lipogenesis via the suppression of LXRα and PXR signaling. |
url |
http://dx.doi.org/10.1155/2019/9401648 |
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