The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
David D Moore - One of the best experts on this subject based on the ideXlab platform.
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Antidiabetic actions of a phosphatidylcholine ligand for Nuclear Receptor LRH-1
2016Co-Authors: Jae Man Lee, Yoon Kwang Lee, Jennifer L. Mamrosh, Scott A. Busby, Patrick R, Manish C. Pathak, Eric A. Ortlund, David D MooreAbstract:Nuclear hormone Receptors regulate diverse metabolic pathways and the orphan Nuclear Receptor LRH-1 (NR5A2) regulates bile acid biosynthesis1,2. Structural studies have identified phospholipids as potential LRH-1 ligands3–5, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine, DLPC) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signaling pathway that regulates bile acid metabolism and glucose homeostasis. Increased fat accumulation in the liver, or steatosis, is tightly correlated with insulin resistance and type 2 diabetes6. Modestly elevated bile acid levels decrease steatosis7. Loss of the Nuclear Receptor LRH-1 decreases bile acid levels1,2, suggesting that an LRH-
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elevated copper impairs hepatic Nuclear Receptor function in wilson s disease
Journal of Clinical Investigation, 2015Co-Authors: Clavia Ruth Wootonkee, Ajay K Jain, Martin Wagner, Michael A Grusak, Milton J Finegold, Svetlana Lutsenko, David D MooreAbstract:: Wilson's disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of complications, including steatosis, cholestasis, cirrhosis, and liver failure. Similar to patients with WD, Atp7b⁻/⁻ mice have markedly elevated levels of hepatic copper and liver pathology. Previous studies have demonstrated that replacement of zinc in the DNA-binding domain of the estrogen Receptor (ER) with copper disrupts specific binding to DNA response elements. Here, we found decreased binding of the Nuclear Receptors FXR, RXR, HNF4α, and LRH-1 to promoter response elements and decreased mRNA expression of Nuclear Receptor target genes in Atp7b⁻/⁻ mice, as well as in adult and pediatric WD patients. Excessive hepatic copper has been described in progressive familial cholestasis (PFIC), and we found that similar to individuals with WD, patients with PFIC2 or PFIC3 who have clinically elevated hepatic copper levels exhibit impaired Nuclear Receptor activity. Together, these data demonstrate that copper-mediated Nuclear Receptor dysfunction disrupts liver function in WD and potentially in other disorders associated with increased hepatic copper levels.
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a Nuclear Receptor dependent phosphatidylcholine pathway with antidiabetic effects
Nature, 2011Co-Authors: Jae Man Lee, Yoon Kwang Lee, Jennifer L. Mamrosh, Scott A. Busby, Eric A. Ortlund, Patrick R Griffin, Manish Pathak, David D MooreAbstract:Nuclear hormone Receptors regulate diverse metabolic pathways and the orphan Nuclear Receptor LRH-1 (also known as NR5A2) regulates bile acid biosynthesis. Structural studies have identified phospholipids as potential LRH-1 ligands, but their functional relevance is unclear. Here we show that an unusual phosphatidylcholine species with two saturated 12 carbon fatty acid acyl side chains (dilauroyl phosphatidylcholine (DLPC)) is an LRH-1 agonist ligand in vitro. DLPC treatment induces bile acid biosynthetic enzymes in mouse liver, increases bile acid levels, and lowers hepatic triglycerides and serum glucose. DLPC treatment also decreases hepatic steatosis and improves glucose homeostasis in two mouse models of insulin resistance. Both the antidiabetic and lipotropic effects are lost in liver-specific Lrh-1 knockouts. These findings identify an LRH-1 dependent phosphatidylcholine signalling pathway that regulates bile acid metabolism and glucose homeostasis.
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stigmasterol a soy lipid derived phytosterol is an antagonist of the bile acid Nuclear Receptor fxr
Pediatric Research, 2007Co-Authors: Beth A Carter, David D Moore, Olga A Taylor, Daniel R Prendergast, Tracy L Zimmerman, Richard Von Furstenberg, Saul J KarpenAbstract:Stigmasterol, a Soy Lipid–Derived Phytosterol, Is an Antagonist of the Bile Acid Nuclear Receptor FXR
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The orphan Nuclear Receptor SHP regulates PGC-1α expression and energy production in brown adipocytes
Cell metabolism, 2005Co-Authors: Li Wang, Jun Liu, Pradip K. Saha, Jiansheng Huang, Lawrence Chan, Bruce Spiegelman, David D MooreAbstract:Summary Brown adipocytes increase energy production in response to induction of PGC-1α, a dominant regulator of energy metabolism. We have found that the orphan Nuclear Receptor SHP (NR0B2) is a negative regulator of PGC-1α expression in brown adipocytes. Mice lacking SHP show increased basal expression of PGC-1α, increased energy expenditure, and resistance to diet-induced obesity. Increased PGC-1α expression in SHP null brown adipose tissue is not due to β-adrenergic activation, since it is also observed in primary cultures of SHP −/− brown adipocytes that are not exposed to such stimuli. In addition, acute inhibition of SHP expression in cultured wild-type brown adipocytes increases basal PGC-1α expression, and SHP overexpression in SHP null brown adipocytes decreases it. The orphan Nuclear Receptor ERRγ is expressed in BAT and its transactivation of the PGC-1α promoter is potently inhibited by SHP. We conclude that SHP functions as a negative regulator of energy production in BAT.
Weiwei Zhang - One of the best experts on this subject based on the ideXlab platform.
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reprogramming of fibroblasts into induced pluripotent stem cells with orphan Nuclear Receptor esrrb
Nature Cell Biology, 2009Co-Authors: Bo Feng, Jianming Jiang, Petra Kraus, Jiahui Ng, Jianchien Dominic Heng, Yunshen Chan, Weiwei ZhangAbstract:The orphan Nuclear Receptor Esrrb induces reprogramming of mouse embryonic fibroblasts to pluripotent stem cells in cooperation with Oct4 and Sox2.
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reprogramming of fibroblasts into induced pluripotent stem cells with orphan Nuclear Receptor esrrb
Nature Cell Biology, 2009Co-Authors: Bo Feng, Jianming Jiang, Petra Kraus, Jianchien Dominic Heng, Yunshen Chan, Laiping Yaw, Weiwei ZhangAbstract:The dominant effect of transcription factors in imparting expanded potency is best exemplified by the reprogramming of fibroblasts to pluripotent cells using retrovirus-mediated transduction of defined transcription factors. In the murine system, Oct4, Sox2, c-Myc and Klf4 are sufficient to convert fibroblasts to induced pluripotent stem (iPS) cells that have many characteristics of embryonic stem (ES) cells. Here we show that the orphan Nuclear Receptor Esrrb functions in conjunction with Oct4 and Sox2 to mediate reprogramming of mouse embryonic fibroblasts (MEFs) to iPS cells. Esrrb-reprogrammed cells share similar expression and epigenetic signatures as ES cells. These cells are also pluripotent and can differentiate in vitro and in vivo into the three major embryonic cell lineages. Furthermore, these cells contribute to mouse chimaeras and are germline transmissible. In ES cells, Esrrb targets many genes involved in self-renewal and pluripotency. This suggests that Esrrb may mediate reprogramming through the upregulation of ES-cell-specific genes. Our findings also indicate that it is possible to reprogram MEFs without exogenous Klf transcription factors and link a Nuclear Receptor to somatic cell reprogramming.
Jianming Jiang - One of the best experts on this subject based on the ideXlab platform.
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reprogramming of fibroblasts into induced pluripotent stem cells with orphan Nuclear Receptor esrrb
Nature Cell Biology, 2009Co-Authors: Bo Feng, Jianming Jiang, Petra Kraus, Jiahui Ng, Jianchien Dominic Heng, Yunshen Chan, Weiwei ZhangAbstract:The orphan Nuclear Receptor Esrrb induces reprogramming of mouse embryonic fibroblasts to pluripotent stem cells in cooperation with Oct4 and Sox2.
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reprogramming of fibroblasts into induced pluripotent stem cells with orphan Nuclear Receptor esrrb
Nature Cell Biology, 2009Co-Authors: Bo Feng, Jianming Jiang, Petra Kraus, Jianchien Dominic Heng, Yunshen Chan, Laiping Yaw, Weiwei ZhangAbstract:The dominant effect of transcription factors in imparting expanded potency is best exemplified by the reprogramming of fibroblasts to pluripotent cells using retrovirus-mediated transduction of defined transcription factors. In the murine system, Oct4, Sox2, c-Myc and Klf4 are sufficient to convert fibroblasts to induced pluripotent stem (iPS) cells that have many characteristics of embryonic stem (ES) cells. Here we show that the orphan Nuclear Receptor Esrrb functions in conjunction with Oct4 and Sox2 to mediate reprogramming of mouse embryonic fibroblasts (MEFs) to iPS cells. Esrrb-reprogrammed cells share similar expression and epigenetic signatures as ES cells. These cells are also pluripotent and can differentiate in vitro and in vivo into the three major embryonic cell lineages. Furthermore, these cells contribute to mouse chimaeras and are germline transmissible. In ES cells, Esrrb targets many genes involved in self-renewal and pluripotency. This suggests that Esrrb may mediate reprogramming through the upregulation of ES-cell-specific genes. Our findings also indicate that it is possible to reprogram MEFs without exogenous Klf transcription factors and link a Nuclear Receptor to somatic cell reprogramming.
Yunshen Chan - One of the best experts on this subject based on the ideXlab platform.
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reprogramming of fibroblasts into induced pluripotent stem cells with orphan Nuclear Receptor esrrb
Nature Cell Biology, 2009Co-Authors: Bo Feng, Jianming Jiang, Petra Kraus, Jiahui Ng, Jianchien Dominic Heng, Yunshen Chan, Weiwei ZhangAbstract:The orphan Nuclear Receptor Esrrb induces reprogramming of mouse embryonic fibroblasts to pluripotent stem cells in cooperation with Oct4 and Sox2.
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reprogramming of fibroblasts into induced pluripotent stem cells with orphan Nuclear Receptor esrrb
Nature Cell Biology, 2009Co-Authors: Bo Feng, Jianming Jiang, Petra Kraus, Jianchien Dominic Heng, Yunshen Chan, Laiping Yaw, Weiwei ZhangAbstract:The dominant effect of transcription factors in imparting expanded potency is best exemplified by the reprogramming of fibroblasts to pluripotent cells using retrovirus-mediated transduction of defined transcription factors. In the murine system, Oct4, Sox2, c-Myc and Klf4 are sufficient to convert fibroblasts to induced pluripotent stem (iPS) cells that have many characteristics of embryonic stem (ES) cells. Here we show that the orphan Nuclear Receptor Esrrb functions in conjunction with Oct4 and Sox2 to mediate reprogramming of mouse embryonic fibroblasts (MEFs) to iPS cells. Esrrb-reprogrammed cells share similar expression and epigenetic signatures as ES cells. These cells are also pluripotent and can differentiate in vitro and in vivo into the three major embryonic cell lineages. Furthermore, these cells contribute to mouse chimaeras and are germline transmissible. In ES cells, Esrrb targets many genes involved in self-renewal and pluripotency. This suggests that Esrrb may mediate reprogramming through the upregulation of ES-cell-specific genes. Our findings also indicate that it is possible to reprogram MEFs without exogenous Klf transcription factors and link a Nuclear Receptor to somatic cell reprogramming.
Jianchien Dominic Heng - One of the best experts on this subject based on the ideXlab platform.
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reprogramming of fibroblasts into induced pluripotent stem cells with orphan Nuclear Receptor esrrb
Nature Cell Biology, 2009Co-Authors: Bo Feng, Jianming Jiang, Petra Kraus, Jiahui Ng, Jianchien Dominic Heng, Yunshen Chan, Weiwei ZhangAbstract:The orphan Nuclear Receptor Esrrb induces reprogramming of mouse embryonic fibroblasts to pluripotent stem cells in cooperation with Oct4 and Sox2.
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reprogramming of fibroblasts into induced pluripotent stem cells with orphan Nuclear Receptor esrrb
Nature Cell Biology, 2009Co-Authors: Bo Feng, Jianming Jiang, Petra Kraus, Jianchien Dominic Heng, Yunshen Chan, Laiping Yaw, Weiwei ZhangAbstract:The dominant effect of transcription factors in imparting expanded potency is best exemplified by the reprogramming of fibroblasts to pluripotent cells using retrovirus-mediated transduction of defined transcription factors. In the murine system, Oct4, Sox2, c-Myc and Klf4 are sufficient to convert fibroblasts to induced pluripotent stem (iPS) cells that have many characteristics of embryonic stem (ES) cells. Here we show that the orphan Nuclear Receptor Esrrb functions in conjunction with Oct4 and Sox2 to mediate reprogramming of mouse embryonic fibroblasts (MEFs) to iPS cells. Esrrb-reprogrammed cells share similar expression and epigenetic signatures as ES cells. These cells are also pluripotent and can differentiate in vitro and in vivo into the three major embryonic cell lineages. Furthermore, these cells contribute to mouse chimaeras and are germline transmissible. In ES cells, Esrrb targets many genes involved in self-renewal and pluripotency. This suggests that Esrrb may mediate reprogramming through the upregulation of ES-cell-specific genes. Our findings also indicate that it is possible to reprogram MEFs without exogenous Klf transcription factors and link a Nuclear Receptor to somatic cell reprogramming.
