title: The adiponectin receptor homologs in C. elegans promote energy utilization and homeostasis.
abstract: Adiponectin is an adipokine with insulin-sensitising actions in vertebrates. Its receptors, AdipoR1 and AdipoR2, are PAQR-type proteins with 7-transmembrane domains and topologies reversed that of GPCR's, i.e. their C-termini are extracellular. We identified three adiponectin receptor homologs in the nematode C. elegans, named paqr-1, paqr-2 and paqr-3. These are differently expressed in the intestine (the main fat-storing tissue), hypodermis, muscles, neurons and secretory tissues, from which they could exert systemic effects. Analysis of mutants revealed that paqr-1 and -2 are novel metabolic regulators in C. elegans and that they act redundantly but independently from paqr-3. paqr-2 is the most important of the three paqr genes: mutants grow poorly, fail to adapt to growth at low temperature, and have a very high fat content with an abnormal enrichment in long (C20) poly-unsaturated fatty acids when combined with the paqr-1 mutation. paqr-2 mutants are also synthetic lethal with mutations in nhr-49, sbp-1 and fat-6, which are C. elegans homologs of nuclear hormone receptors, SREBP and FAT-6 (a Δ9 desaturase), respectively. Like paqr-2, paqr-1 is also synthetic lethal with sbp-1. Mutations in aak-2, the C. elegans homolog of AMPK, or nhr-80, another nuclear hormone receptor gene, suppress the growth phenotype of paqr-2 mutants, probably because they restore the balance between energy expenditure and storage. We conclude that paqr-1 and paqr-2 are receptors that regulate fatty acid metabolism and cold adaptation in C. elegans, that their main function is to promote energy utilization rather than storage, and that PAQR class proteins have regulated metabolism in metazoans for at least 700 million years.
authors.affiliation: Department of Cell and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Svensson
authors.forename: Louise
authors.initials: L
authors.lastname: Olsen
authors.forename: Catarina
authors.initials: C
authors.lastname: Mörck
authors.forename: Christian
authors.initials: C
authors.lastname: Brackmann
authors.forename: Annika
authors.initials: A
authors.lastname: Enejder
authors.forename: Nils J
authors.initials: NJ
authors.lastname: Faergeman
authors.forename: Marc
authors.initials: M
authors.lastname: Pilon
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000378:metabolism* / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004032:Diet; D004734:Energy Metabolism / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D010802:Phylogeny; D020033:Protein Isoforms / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D054419:Receptors, Adiponectin / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D020033:Protein Isoforms; D054419:Receptors, Adiponectin; D011993:Recombinant Fusion Proteins