the adiponectin receptor homologs in c. elegans promote energy utilization and homeostasis脂联素受体同源染色体在秀丽隐杆线虫提高能源利用率和体内平衡.pdfVIP

The Adiponectin Receptor Homologs in C. elegans Promote Energy Utilization and Homeostasis 1 2 ¨ 1¤ 3 3 Emma Svensson , Louise Olsen , Catarina Morck , Christian Brackmann , Annika Enejder , Nils J. 2 1 Faergeman , Marc Pilon * 1 Department of Cell and Molecular Biology, University of Gothenburg, Gothenburg, Sweden, 2 Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, 3 Department of Chemical and Biological Engineering, Chalmers University, Gothenburg, Sweden 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,