2-Arachydonoylglycerol as a metabolic signal which coordinates lipid synthesis and life cycle in C. elegans.

PREZ, G. M.; GALLES, C.; KURZCHALIA, T.; DE MENDOZA, D.

Puerto Iguazú

Congreso; 56th International Conference on the Bioscience of Lipids.; 2015

2-Arachydonoylglycerol as a metabolic signal which coordinates lipid synthesis and life cycle in C. elegansPolyunsaturated fatty acids (PUFAs) and branched-chain fatty acids (BCFAs) are important membrane components and precursors of signaling molecules. To investigate the role that PUFAS and BCFAs play in C. elegans dauer diapause, we suppressed the biosynthesis of these fatty acids by using RNA interference against let-767, a major 3-ketoacyl-CoA reductase, in dauer constitutive TGF-beta mutants at 20°C (the semi-permissive temperature). We found that let-767 RNAi enhances the formation of dauers in daf-7(e1372) animals and this arrest can be overcome by feeding the animals with 2-arachydonoylglycerol (2-AG), an important endocannabinoid (eCB) involved in several aspects of mammalian physiology and pathology. Moreover, we found that 2-AG exerts its effect in a dose-dependent manner. We also show, using the LC-MS/MS technique, that this endocannabinoid is indeed synthesized by wild type worms, but not by mutant fat-3(ok1126), which lacks one the enzymes needed to synthesize arachydonic acid, one of the structural components of 2-AG. These results indicate that 2-AG represents a signal that coordinates the status of long-chain fatty acid synthesis with metabolic changes that ultimately determine the decision between diapause and reproduction in C. elegans.