RRC ID 46733
著者 Liang B, Ferguson K, Kadyk L, Watts JL.
タイトル The role of nuclear receptor NHR-64 in fat storage regulation in Caenorhabditis elegans.
ジャーナル PLoS One
Abstract 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.
巻・号 5(3)
ページ e9869
公開日 2010-3-25
DOI 10.1371/journal.pone.0009869
PMID 20360843
PMC PMC2845610
MeSH Acetyl-CoA Carboxylase / metabolism* Alleles Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Fatty Acids / chemistry Gene Expression Regulation* Homeostasis Lipids / chemistry Mitochondria / metabolism Mutation* Peroxisomes / metabolism RNA Interference Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / physiology* Stearic Acids / chemistry Transcription, Genetic*
IF 2.74
引用数 31
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm1106 tm331 tm2206