Hepatic Cerebroside Sulfotransferase Is Induced by PPARα Activation in Mice

Sulfatides are one of the major sphingoglycolipids in mammalian serum and are synthesized and secreted mainly from the liver as a component of lipoproteins. Recent studies revealed a protective role for serum sulfatides against arteriosclerosis and hypercoagulation. Although peroxisome proliferator-...

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Main Authors: Takefumi Kimura, Takero Nakajima, Yuji Kamijo, Naoki Tanaka, Lixuan Wang, Atsushi Hara, Eiko Sugiyama, Eiji Tanaka, Frank J. Gonzalez, Toshifumi Aoyama
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2012/174932
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author Takefumi Kimura
Takero Nakajima
Yuji Kamijo
Naoki Tanaka
Lixuan Wang
Atsushi Hara
Eiko Sugiyama
Eiji Tanaka
Frank J. Gonzalez
Toshifumi Aoyama
author_facet Takefumi Kimura
Takero Nakajima
Yuji Kamijo
Naoki Tanaka
Lixuan Wang
Atsushi Hara
Eiko Sugiyama
Eiji Tanaka
Frank J. Gonzalez
Toshifumi Aoyama
author_sort Takefumi Kimura
collection DOAJ
description Sulfatides are one of the major sphingoglycolipids in mammalian serum and are synthesized and secreted mainly from the liver as a component of lipoproteins. Recent studies revealed a protective role for serum sulfatides against arteriosclerosis and hypercoagulation. Although peroxisome proliferator-activated receptor (PPAR) α has important functions in hepatic lipoprotein metabolism, its association with sulfatides has not been investigated. In this study, sulfatide levels and the expression of enzymes related to sulfatide metabolism were examined using wild-type (+/+), Ppara-heterozygous (+/−), and Ppara-null (−/−) mice given a control diet or one containing 0.1% fenofibrate, a clinically used hypolipidemic drug and PPARα activator. Fenofibrate treatment increased serum and hepatic sulfatides in Ppara (+/+) and (+/−) mice through a marked induction of hepatic cerebroside sulfotransferase (CST), a key enzyme in sulfatide synthesis, in a PPARα-dependent manner. Furthermore, increases in CST mRNA levels were correlated with mRNA elevations of several known PPARα target genes, and such changes were not observed for other sulfatide-metabolism enzymes in the liver. These results suggest that PPARα activation enhances hepatic sulfatide synthesis via CST induction and implicate CST as a novel PPARα target gene.
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spelling doaj-art-eeb6d13042e54a7ea9fb749c3d6a166e2025-02-03T06:11:45ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/174932174932Hepatic Cerebroside Sulfotransferase Is Induced by PPARα Activation in MiceTakefumi Kimura0Takero Nakajima1Yuji Kamijo2Naoki Tanaka3Lixuan Wang4Atsushi Hara5Eiko Sugiyama6Eiji Tanaka7Frank J. Gonzalez8Toshifumi Aoyama9Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanDepartment of Nutritional Science, Nagano Prefectural College, Nagano 380-8525, JapanDepartment of Gastroenterology, Shinshu University School of Medicine, Matsumoto 390-8621, JapanLaboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USADepartment of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, JapanSulfatides are one of the major sphingoglycolipids in mammalian serum and are synthesized and secreted mainly from the liver as a component of lipoproteins. Recent studies revealed a protective role for serum sulfatides against arteriosclerosis and hypercoagulation. Although peroxisome proliferator-activated receptor (PPAR) α has important functions in hepatic lipoprotein metabolism, its association with sulfatides has not been investigated. In this study, sulfatide levels and the expression of enzymes related to sulfatide metabolism were examined using wild-type (+/+), Ppara-heterozygous (+/−), and Ppara-null (−/−) mice given a control diet or one containing 0.1% fenofibrate, a clinically used hypolipidemic drug and PPARα activator. Fenofibrate treatment increased serum and hepatic sulfatides in Ppara (+/+) and (+/−) mice through a marked induction of hepatic cerebroside sulfotransferase (CST), a key enzyme in sulfatide synthesis, in a PPARα-dependent manner. Furthermore, increases in CST mRNA levels were correlated with mRNA elevations of several known PPARα target genes, and such changes were not observed for other sulfatide-metabolism enzymes in the liver. These results suggest that PPARα activation enhances hepatic sulfatide synthesis via CST induction and implicate CST as a novel PPARα target gene.http://dx.doi.org/10.1155/2012/174932
spellingShingle Takefumi Kimura
Takero Nakajima
Yuji Kamijo
Naoki Tanaka
Lixuan Wang
Atsushi Hara
Eiko Sugiyama
Eiji Tanaka
Frank J. Gonzalez
Toshifumi Aoyama
Hepatic Cerebroside Sulfotransferase Is Induced by PPARα Activation in Mice
PPAR Research
title Hepatic Cerebroside Sulfotransferase Is Induced by PPARα Activation in Mice
title_full Hepatic Cerebroside Sulfotransferase Is Induced by PPARα Activation in Mice
title_fullStr Hepatic Cerebroside Sulfotransferase Is Induced by PPARα Activation in Mice
title_full_unstemmed Hepatic Cerebroside Sulfotransferase Is Induced by PPARα Activation in Mice
title_short Hepatic Cerebroside Sulfotransferase Is Induced by PPARα Activation in Mice
title_sort hepatic cerebroside sulfotransferase is induced by pparα activation in mice
url http://dx.doi.org/10.1155/2012/174932
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