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 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.
Liang
Bin
B
School of Molecular Biosciences, Washington State University, Pullman, Washington, United States of America.
Ferguson
Kim
K
Kadyk
Lisa
L
Watts
Jennifer L
JL
D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D005227:Fatty Acids / Q000737:chemistry; D005786:Gene Expression Regulation; D006706:Homeostasis; D008055:Lipids / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D020675:Peroxisomes / Q000378:metabolism; D034622:RNA Interference; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D013229:Stearic Acids / Q000737:chemistry; D014158:Transcription, Genetic
D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; D008055:Lipids; C554841:NHR-64 protein, C elegans; D018160:Receptors, Cytoplasmic and Nuclear; D013229:Stearic Acids; D000103:Acetyl-CoA Carboxylase