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 |