On the tracks of endocannabinoids in C. elegans

EXEQUIEL O. J. PORTA; GASTÓN PREZ; GUILLERMO R. LABADIE; JULIA FERNÁNDEZ DE LUCO; DIEGO DE MENDOZA; JAIME A. ISERN; CELINA GALLES

Buzios

Simposio; BrazMedChem 2016; 2016

BrazMedChem

Fatty Acids are highly variable in their structures, and these variations greatly contribute to the vast diversity that exists in lipid architectures. We have recently found that down-regulation of de novo fatty acid synthesis in the nematode C. elegans alters its developmental program to enter a state of larval arrest, named dauer diapause, which is a long-lived stress-resistant stage. Furthermore, we found that the addition of two exogenous endocannabinoids(eCBs), 2-arachidonylglycerol (2AG) and Anandamide (AEA), prevents this dauer arrest, induced by deprivation of lipid synthesis, and promotes reproductive growth. Like most invertebrates, this animal does not present sequences homologous to mammalian cannabinoid receptor proteins. These findings thus provide a tractable system for investigating the mechanisms of eCB-mediated control of nutrient intake and energy balance.With the purpose to reveal the mystery of the activity of endocanabinoides in C. elegans, a focus library of 32 new analogs inspired on the neurotransmisor 2-AG and one of its biosynthetic immediate precursors (1,2-diacylglycerol).The collection was prepared using 8 different fatty acids (nonanoic, lauric, palmitic, estearic, oleic, linoleic, linolenic and arachidonic acis). The activity of the prepared compounds was assayed as C. elegans dauer diapause disruptor in wild type nematods (N2) and genetically modified nematods to control the entering to the dormant dauer larva stage (daf-7 and daf-2). Additionally, compounds were assayed on fat-3, that the has controlled levels of fatty acids and do not synthesis arachidonic acid.