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

• Published in: PloS one 2010-03, Vol.5 (3), p.e9869
• Main Authors: Liang, Bin, Ferguson, Kim, Kadyk, Lisa, Watts, Jennifer L
• Format: Article
• Language: English
• Subjects: Acetyl-CoA carboxylase; Acetyl-CoA Carboxylase - metabolism; Acyl-CoA oxidase; Alleles; Animals; Biosynthesis; Caenorhabditis elegans; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - physiology; Cell Biology/Developmental Molecular Mechanisms; Chain branching; Cholesterol; Deactivation; Defects; Desaturase; Diabetes; Diet; Drosophila melanogaster; Fatty acid composition; Fatty acids; Fatty Acids - chemistry; Gene expression; Gene Expression Regulation; Genes; Genetic engineering; Genetics and Genomics/Disease Models; Genetics and Genomics/Gene Expression; Genetics and Genomics/Gene Function; Genomes; Growth rate; Homeostasis; Homology; Inactivation; Insects; Ligands; Lipid metabolism; Lipids; Lipids - chemistry; Low fat; Mammals; Metabolism; Mitochondria; Mitochondria - metabolism; Mutants; Mutation; Nematodes; Nuclear receptors; Nutrition/Obesity; Oxidases; Oxidation; Peroxisomes; Peroxisomes - metabolism; Physiological aspects; Protein binding; Receptors; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - physiology; Ribonucleic acid; RNA; RNA Interference; RNA-mediated interference; Rodents; Stearic Acids - chemistry; Stearoyl-CoA desaturase; Sterol regulatory element-binding protein; Storage; Transcription; Transcription factors; Transcription, Genetic; Worms; Yeast
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009869

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.