Free long chain fatty acid solitarily primes early postembryonic development in Caenorhabditis elegans under starvation

Postembryonic development of animals is long considered an internal predetermined program, while macronutrient is essential only because they provide biomatters and energy to support this process. However, in this study, by using a nematode Caenorhabditis elegans model, we surprisingly found that dietary supplementation of palmitic acid alone, but not other essential nutrients of abundance such as glucose or amino acid mixture, sufficiently initiated the early postembryonic development under complete macronutrient deprivation. Such a development was indicated by changes in morphology, cellular markers in multiple tissues, behaviors and the global transcription pattern. Mechanistically, palmitate doesnt function as a biomatter/energy provider, but as a ligand to activate the nuclear hormone receptor NHR-49/80 and generate an obscure peroxisome-derived secretive hormone in the intestine. Such a hormonal signal was received by chemosensory neurons in the head in regulating the insulin-like neuropeptide secretion and its downstream nuclear receptor to orchestrate the global development. Moreover, the nutrient-sensing hub mTORC1 played a negative role in this process. In conclusion, our data indicate that free fatty acid acts as a prime nutrient signal to launch the early development in C. elegans; and implicate that specific nutrient rather than the internal genetic program is the first impetus of postembryonic development.