The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans

Bin Liang; Kim Ferguson; Lisa Kadyk; Jennifer L Watts

doi:10.1371/journal.pone.0009869

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The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans

Journal article

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The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans

Bin Liang, Kim Ferguson, Lisa Kadyk and Jennifer L Watts

PloS one, Vol.5(3), pp.e9869-e9869

03/25/2010

DOI: https://doi.org/10.1371/journal.pone.0009869

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https://hdl.handle.net/2376/115895

PMCID: PMC2845610

PMID: 20360843

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Abstract

Fatty Acids - chemistry

Gene Expression Regulation

Homeostasis

Receptors, Cytoplasmic and Nuclear - physiology

Mitochondria - metabolism

Receptors, Cytoplasmic and Nuclear - genetics

Stearic Acids - chemistry

Peroxisomes - metabolism

Caenorhabditis elegans

Lipids - chemistry

Animals

RNA Interference

Alleles

Transcription, Genetic

Caenorhabditis elegans Proteins - physiology

Mutation

Caenorhabditis elegans Proteins - genetics

Acetyl-CoA Carboxylase - metabolism

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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Title: The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans
Creators: Bin Liang - School of Molecular Biosciences, Washington State University, Pullman, Washington, United States of America
Kim Ferguson
Lisa Kadyk
Jennifer L Watts
Publication Details: PloS one, Vol.5(3), pp.e9869-e9869
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: R01DK74114 / NIDDK NIH HHS R01 DK074114 / NIDDK NIH HHS
Identifiers: 99900547827501842
Language: English
Resource Type: Journal article