Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation

In cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum c...

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Main Authors: Yun Bin Lee, Jong Ho Choi, Eun Nam Kim, Jin Seok, Hyun-Jung Lee, Jung-Hwan Yoon, Gi Jin Kim
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2017/5180579
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author Yun Bin Lee
Jong Ho Choi
Eun Nam Kim
Jin Seok
Hyun-Jung Lee
Jung-Hwan Yoon
Gi Jin Kim
author_facet Yun Bin Lee
Jong Ho Choi
Eun Nam Kim
Jin Seok
Hyun-Jung Lee
Jung-Hwan Yoon
Gi Jin Kim
author_sort Yun Bin Lee
collection DOAJ
description In cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum cholesterol level, which was elevated after BDL, was significantly decreased following CP-MSC transplantation. The expression levels of genes involved in intracellular lipid uptake, including long-chain fatty acyl-CoA synthetases and fatty acid transport proteins, were decreased in rats after BDL; however, they were not significantly changed by subsequent CP-MSC transplantation. Carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in mitochondrial β-oxidation, was upregulated after BDL and then was downregulated after CP-MSC transplantation. CPT1A expression was changed via microRNA-33—a posttranscriptional regulator of CPT1A—in a peroxisome proliferator-activated receptor α-independent manner. Cellular adenosine triphosphate production—an indicator of mitochondrial function—was reduced after BDL and was restored by CP-MSC transplantation. Expression levels of heme oxygenases also were significantly affected following BDL and CP-MSC transplantation. Lipid metabolism is altered in response to chronic cholestatic liver injury and can be restored by CP-MSC transplantation. Our study findings support the therapeutic potential of CP-MSCs in cholestatic liver diseases and help in understanding the fundamental mechanisms by which CP-MSCs affect energy metabolism.
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spelling doaj-art-fd9ddc638d544464a17a9894d4c94b242025-02-03T01:07:27ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/51805795180579Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct LigationYun Bin Lee0Jong Ho Choi1Eun Nam Kim2Jin Seok3Hyun-Jung Lee4Jung-Hwan Yoon5Gi Jin Kim6Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of KoreaDepartment of Biomedical Science, CHA University, Seongnam, Republic of KoreaDepartment of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of KoreaDepartment of Biomedical Science, CHA University, Seongnam, Republic of KoreaDepartment of Biomedical Science, CHA University, Seongnam, Republic of KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Biomedical Science, CHA University, Seongnam, Republic of KoreaIn cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum cholesterol level, which was elevated after BDL, was significantly decreased following CP-MSC transplantation. The expression levels of genes involved in intracellular lipid uptake, including long-chain fatty acyl-CoA synthetases and fatty acid transport proteins, were decreased in rats after BDL; however, they were not significantly changed by subsequent CP-MSC transplantation. Carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in mitochondrial β-oxidation, was upregulated after BDL and then was downregulated after CP-MSC transplantation. CPT1A expression was changed via microRNA-33—a posttranscriptional regulator of CPT1A—in a peroxisome proliferator-activated receptor α-independent manner. Cellular adenosine triphosphate production—an indicator of mitochondrial function—was reduced after BDL and was restored by CP-MSC transplantation. Expression levels of heme oxygenases also were significantly affected following BDL and CP-MSC transplantation. Lipid metabolism is altered in response to chronic cholestatic liver injury and can be restored by CP-MSC transplantation. Our study findings support the therapeutic potential of CP-MSCs in cholestatic liver diseases and help in understanding the fundamental mechanisms by which CP-MSCs affect energy metabolism.http://dx.doi.org/10.1155/2017/5180579
spellingShingle Yun Bin Lee
Jong Ho Choi
Eun Nam Kim
Jin Seok
Hyun-Jung Lee
Jung-Hwan Yoon
Gi Jin Kim
Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation
Stem Cells International
title Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation
title_full Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation
title_fullStr Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation
title_full_unstemmed Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation
title_short Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation
title_sort human chorionic plate derived mesenchymal stem cells restore hepatic lipid metabolism in a rat model of bile duct ligation
url http://dx.doi.org/10.1155/2017/5180579
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