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The Role of Nuclear Receptor NHR-64 in Fat Storage Regulation in Caenorhabditis elegans

Nuclear hormone receptors (NHRs) play vital roles in the regulation of metabolism, reproduction, and development. We found that inactivation of a C. elegans HNF4 homologue nhr-64 by RNA interference (RNAi) suppresses low fat stores in stearoyl-CoA desaturase-deficient fat-6;fat-7 double mutants and...

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Autores principales: Liang, Bin, Ferguson, Kim, Kadyk, Lisa, Watts, Jennifer L.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845610/
https://www.ncbi.nlm.nih.gov/pubmed/20360843
http://dx.doi.org/10.1371/journal.pone.0009869
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author Liang, Bin
Ferguson, Kim
Kadyk, Lisa
Watts, Jennifer L.
author_facet Liang, Bin
Ferguson, Kim
Kadyk, Lisa
Watts, Jennifer L.
author_sort Liang, Bin
collection PubMed
description Nuclear hormone receptors (NHRs) play vital roles in the regulation of metabolism, reproduction, and development. We found that inactivation of a C. elegans HNF4 homologue nhr-64 by RNA interference (RNAi) suppresses low fat stores in stearoyl-CoA desaturase-deficient fat-6;fat-7 double mutants and sterol regulatory element binding protein (SREBP) sbp-1 mutants. Furthermore, inactivation of nhr-64 improves the growth rate of the fat-6;fat-7and sbp-1 strains. While nhr-64RNAi subtly affects fatty acid composition and fat storage in wild-type C. elegans, its effects on lipid metabolism are most apparent in the background of stearoyl-CoA desaturase or SREBP deficiency. NHR-64 displays transcriptional activating activity when expressed in yeast, and inactivation of nhr-64 affects the expression of at least 14 metabolic genes. Wild-type worms treated with nhr-64 RNAi display increased expression of acetyl-CoA carboxylase as well as increased abundance of de novo synthesized monomethyl branched chain fatty acids, suggesting an increase in fat synthesis. However, reduced expression of the acetyl-CoA synthetase gene acs-2 and an acyl-CoA oxidase gene indicates that a key role of NHR-64 may be to promote fatty acid oxidation in mitochondria and peroxisomes. These studies reveal that NHR-64 is an important regulator of fat storage in C. elegans.
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spelling pubmed-28456102010-04-01 The Role of Nuclear Receptor NHR-64 in Fat Storage Regulation in Caenorhabditis elegans Liang, Bin Ferguson, Kim Kadyk, Lisa Watts, Jennifer L. PLoS One Research Article Nuclear hormone receptors (NHRs) play vital roles in the regulation of metabolism, reproduction, and development. We found that inactivation of a C. elegans HNF4 homologue nhr-64 by RNA interference (RNAi) suppresses low fat stores in stearoyl-CoA desaturase-deficient fat-6;fat-7 double mutants and sterol regulatory element binding protein (SREBP) sbp-1 mutants. Furthermore, inactivation of nhr-64 improves the growth rate of the fat-6;fat-7and sbp-1 strains. While nhr-64RNAi subtly affects fatty acid composition and fat storage in wild-type C. elegans, its effects on lipid metabolism are most apparent in the background of stearoyl-CoA desaturase or SREBP deficiency. NHR-64 displays transcriptional activating activity when expressed in yeast, and inactivation of nhr-64 affects the expression of at least 14 metabolic genes. Wild-type worms treated with nhr-64 RNAi display increased expression of acetyl-CoA carboxylase as well as increased abundance of de novo synthesized monomethyl branched chain fatty acids, suggesting an increase in fat synthesis. However, reduced expression of the acetyl-CoA synthetase gene acs-2 and an acyl-CoA oxidase gene indicates that a key role of NHR-64 may be to promote fatty acid oxidation in mitochondria and peroxisomes. These studies reveal that NHR-64 is an important regulator of fat storage in C. elegans. Public Library of Science 2010-03-25 /pmc/articles/PMC2845610/ /pubmed/20360843 http://dx.doi.org/10.1371/journal.pone.0009869 Text en Liang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Liang, Bin
Ferguson, Kim
Kadyk, Lisa
Watts, Jennifer L.
The Role of Nuclear Receptor NHR-64 in Fat Storage Regulation in Caenorhabditis elegans
title The Role of Nuclear Receptor NHR-64 in Fat Storage Regulation in Caenorhabditis elegans
title_full The Role of Nuclear Receptor NHR-64 in Fat Storage Regulation in Caenorhabditis elegans
title_fullStr The Role of Nuclear Receptor NHR-64 in Fat Storage Regulation in Caenorhabditis elegans
title_full_unstemmed The Role of Nuclear Receptor NHR-64 in Fat Storage Regulation in Caenorhabditis elegans
title_short The Role of Nuclear Receptor NHR-64 in Fat Storage Regulation in Caenorhabditis elegans
title_sort role of nuclear receptor nhr-64 in fat storage regulation in caenorhabditis elegans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845610/
https://www.ncbi.nlm.nih.gov/pubmed/20360843
http://dx.doi.org/10.1371/journal.pone.0009869
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