Hepatic Cerebroside Sulfotransferase Is Induced by PPARα Activation in Mice
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- Takefumi Kimura
- Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
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- Takero Nakajima
- Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
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- Yuji Kamijo
- Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
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- Naoki Tanaka
- Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
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- Lixuan Wang
- Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
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- Atsushi Hara
- Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
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- Eiko Sugiyama
- Department of Nutritional Science, Nagano Prefectural College, Nagano 380-8525, Japan
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- Eiji Tanaka
- Department of Gastroenterology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
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- Frank J. Gonzalez
- Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
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- Toshifumi Aoyama
- Department of Metabolic Regulation, Institute on Aging and Adaptation, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
Description
<jats:p>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)<jats:italic>α</jats:italic>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 (+/+),<jats:italic>Ppara</jats:italic>-heterozygous (+/−), and<jats:italic>Ppara</jats:italic>-null (−/−) mice given a control diet or one containing 0.1% fenofibrate, a clinically used hypolipidemic drug and PPAR<jats:italic>α</jats:italic>activator. Fenofibrate treatment increased serum and hepatic sulfatides in<jats:italic>Ppara</jats:italic>(+/+) and (+/−) mice through a marked induction of hepatic cerebroside sulfotransferase (CST), a key enzyme in sulfatide synthesis, in a PPAR<jats:italic>α</jats:italic>-dependent manner. Furthermore, increases in CST mRNA levels were correlated with mRNA elevations of several known PPAR<jats:italic>α</jats:italic>target genes, and such changes were not observed for other sulfatide-metabolism enzymes in the liver. These results suggest that PPAR<jats:italic>α</jats:italic>activation enhances hepatic sulfatide synthesis via CST induction and implicate CST as a novel PPAR<jats:italic>α</jats:italic>target gene.</jats:p>
Journal
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- PPAR Research
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PPAR Research 2012 1-10, 2012
Hindawi Limited
