A Caenorhabditis elegans nutrient response system partially dependent on nuclear receptor NHR-49.
Appropriate response to nutritional stress is critical for animal survival and metabolic health. To better understand regulatory networks that sense and respond to nutritional availability, we developed a quantitative RT-PCR strategy to monitor changes in metabolic gene expression resulting from short-term food deprivation (fasting) in Caenorhabditis elegans. Examining 97 fat and glucose metabolism genes in fed and fasted animals, we identified 18 genes significantly influenced by food withdrawal in all developmental stages. Fasting response genes fell into multiple kinetic classes, with some genes showing significant activation or repression just 1 h after food was removed. As expected, fasting stimulated the expression of genes involved in mobilizing fats for energy production, including mitochondrial beta-oxidation genes. Surprisingly, however, we found that other mitochondrial beta-oxidation genes were repressed by food deprivation. Fasting also affected genes involved in mono- and polyunsaturated fatty acid synthesis: four desaturases were induced, and one stearoyl-CoA desaturase (SCD) was strongly repressed. Accordingly, fasted animals displayed considerable changes in fatty acid composition. Finally, nuclear receptor nhr-49 played a key role in nutritional response, enabling induction of beta-oxidation genes upon food deprivation and facilitating activation of SCD in fed animals. Our characterization of a fasting response system and our finding that nhr-49 regulates a sector within this system provide insight into the mechanisms by which animals respond to nutritional signals.
Van Gilst
Marc R
MR
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143-2280, USA.
Hadjivassiliou
Haralambos
H
Yamamoto
Keith R
KR
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis* / Q000235:genetics; D005231:Fatty Acids, Unsaturated / Q000096:biosynthesis; D005508:Food Deprivation / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction / Q000502:physiology*; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D005231:Fatty Acids, Unsaturated; C505159:NHR-49 protein, C elegans; D018160:Receptors, Cytoplasmic and Nuclear; D013230:Stearoyl-CoA Desaturase