The Nuclear Receptor DAF-12 Regulates Nutrient Metabolism and Reproductive Growth in Nematodes

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Animals adjust their internal biological processes in response to their environments. In this study, we report that in a nutrient rich environment the free-living nematode, Caenorhabditis elegans, induces an energy-generating metabolic pathway to govern its reproductive growth by activating the nuclear receptor, DAF-12. By responding to its endogenous ligands, called dafachronic acids, DAF-12 induces oxidation of lipids to produce the energy necessary to support growth and reproduction; and likewise, in the absence of dafachronic acids, DAF-12 prevents activation of this pathway. Through gene expression analysis, we show that DAF-12 regulates a network of genes involved in energy homeostasis and lipid metabolism. Given that dafachronic acids are produced only in well-fed worms, we conclude that DAF-12 functions as an environmental sensor that coordinately governs energy homeostasis. Through analogous studies in the incurable human parasite, Strongyloides stercoralis, we demonstrate that this pathway is conserved and that blocking it compromises the viability of the parasites. These findings elucidate a molecular mechanism for how nematodes govern their energy needs in response to the environment, and provide a potential new strategy for treating nematode parasitic diseases.

Vyšlo v časopise: The Nuclear Receptor DAF-12 Regulates Nutrient Metabolism and Reproductive Growth in Nematodes. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005027
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005027

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