Fatty acid metabolic reprogramming promotesC. elegansdevelopment

AbstractAcetylcholine signaling has been reported to play essential roles in animal metabolic regulation and disease affected by diets. However, the underlying mechanisms that how diets regulate animal physiology and health are not well understood. Here we found that the acetylcholine receptor geneeat-2was expressed in most of the pharyngeal muscles, which is in accordance to our previous report that EAT-2 received synaptic signals not only from pharyngeal MC neurons. The expression of fatty acid synthesis genes was significantly increased in botheat-2andtmc-1fast-growth mutants on CeMM food environment, compared to the wild-type. Excitingly, dietary fatty acids such as 15-methyl-hexadecanoic acid (C17ISO), palmitic acid (PA, C16:0) and stearic acid (SA, C18:0) supplementation, significantly accelerated wild-type worm development on CeMM, indicating that the fatty acid synthesis reprogramming is an essential strategy forC. elegansto regulate its development and growth on CeMM diet. Furthermore, we found that fatty acid elongase geneelo-6knock-out significantly attenuatedeat-2mutant’ fast growth, while overexpression ofelo-6could rescue theeat-2; elo-6double mutant’ slow development, which suggested thatelo-6played a major role in the above metabolic remodeling. Taken together, our report indicates that diets regulate neuromuscular circuit and modulateC. elegansdevelopment via fatty acid metabolic reprogramming. As most of the key genes and metabolites found in this study are conserved in both invertebrate and vertebrate animals, we believed that our results might provide essential clues to the molecular mechanisms underlying interactions among animal nutrition sensation, metabolism reprogramming and developmental regulation.Significance StatementDiets and nutritional composition affect animal development and human health, however the underlying mechanisms remain elusive. We demonstrate that the acetylcholine receptor geneeat-2is expressed in most of pharyngeal muscles, and the expression of fatty acid synthesis genes is significantly increased in botheat-2andtmc-1fast-growth mutants on the synthetic chemical defined CeMM food environment. Dietary supplementation of several fatty acids significantly speed up animal development. Furthermore, we demonstrate that the fatty acid elongase geneelo-6knock-out attenuateseat-2mutant’ fast growth, and overexpression of wild-typeelo-6promotes theeat-2; elo-6double mutant’ slow development. Our findings describe that acetylcholine signaling coordinate nutrition sensation and developmental regulation through fatty acid metabolic remodeling.