The Adiponectin Receptor Homologs in C-elegans Promote Energy Utilization and Homeostasis
Artikel i vetenskaplig tidskrift, 2011

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 Delta 9 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.

mice

migrations

adipose-specific protein

activated protein-kinase

daf-16

storage

weight

obesity

nematode caenorhabditis-elegans

fatty-acid-composition

Författare

E. Svensson

Göteborgs universitet

L. Olsen

University of Southern Denmark

Catarina Mörck

University of California

Göteborgs universitet

Christian Brackmann

Chalmers, Kemi- och bioteknik, Molekylär mikroskopi

Annika Enejder

Chalmers, Kemi- och bioteknik, Molekylär mikroskopi

N. J. Faergeman

University of Southern Denmark

Marc Pilon

Göteborgs universitet

PLoS ONE

1932-6203 (ISSN)

Vol. 6 6 e21343

Ämneskategorier

Biologiska vetenskaper

DOI

10.1371/journal.pone.0021343