PRY-1/Axin signaling regulates lipid metabolism in Caenorhabditis elegans

Abstract

The nematode Caenorhabditis elegans is a leading animal model to study how signaling pathway components function in conserved biological processes. Here, we describe the role of an Axin family member, pry-1, in lipid metabolism. As a central component of the canonical Wnt signaling pathway, pry-1 acts as a scaffold to multiprotein destruction complex that negatively regulates the expression of Wnt target genes. A genome-wide transcriptome profiling of pry-1 mutant revealed genes associated with aging and lipid metabolism such as vitellogenins (yolk lipoproteins), fatty acid desaturases, lipases, and fatty acid transporters. Consistent with this we found that pry-1 is crucial for the normal adult lifespan and maintenance of lipid levels. Knock-downs of vit genes in pry-1 mutant background restored lipid levels, suggesting that Vitellogenins contribute to PRY-1 function in lipid metabolic processes. Additionally, lowered expression of desaturases and lipidomics analysis provided evidence that the fatty acid synthesis is reduced in pry-1 mutants. In agreement with this an exogenous supply of oleic acid restored depleted lipids in somatic tissues of worms. Overall, our findings demonstrate that PRY-1/Axin signaling is essential for lipid metabolism and involves regulation of yolk proteins.