School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
PLoS Biol. 2024 Oct 22;22(10):e3002841. doi: 10.1371/journal.pbio.3002841. eCollection 2024 Oct.
Postembryonic development of animals has long been considered an internally predetermined program, while macronutrients were believed to be essential solely for providing biomatters and energy to support this process. However, in this study, by using a nematode Caenorhabditis elegans (abbreviated as C. elegans hereafter) model, we surprisingly discovered that dietary supplementation of palmitic acid alone, rather than other abundant essential nutrients such as glucose or amino acid mixture, was sufficient to initiate early postembryonic development even under complete macronutrient deprivation. Such a development was evidenced by changes in morphology, cellular markers in multiple tissues, behaviors, and the global transcription pattern and it occurred earlier than the well-known early L1 nutrient checkpoint. Mechanistically, palmitic acid did not function as a biomatter/energy provider, but rather as a ligand to activate the nuclear hormone receptor NHR-49/80, leading to the production of an unknown peroxisome-derived secretive hormone in the intestine. This hormonal signal was received by chemosensory neurons in the head, regulating the insulin-like neuropeptide secretion and its downstream nuclear receptor to orchestrate global development. Additionally, the nutrient-sensing hub mTORC1 played a negative role in this process. In conclusion, our data indicate that free fatty acids act as a primary nutrient signal to launch the early development in C. elegans, which suggests that specific nutrients, rather than the internal genetic program, serve as the first impetus for postembryonic development.
动物的胚胎后发育长期以来被认为是一个内在预定的程序，而大量营养素被认为是提供生物物质和能量以支持这一过程所必需的。然而，在这项研究中，通过使用线虫秀丽隐杆线虫（简称 C. elegans）模型，我们令人惊讶地发现，单独补充棕榈酸，而不是其他丰富的必需营养素，如葡萄糖或氨基酸混合物，足以启动早期胚胎后发育，即使在完全缺乏大量营养素的情况下也是如此。这种发育表现为形态变化、多个组织中的细胞标志物、行为以及全局转录模式的变化，而且比众所周知的早期 L1 营养检查点更早发生。从机制上讲，棕榈酸不作为生物物质/能量提供物，而是作为激活核激素受体 NHR-49/80 的配体，导致在肠道中产生未知的过氧化物酶体衍生的分泌激素。这种激素信号被头部的化学感觉神经元接收，调节胰岛素样神经肽的分泌及其下游核受体，以协调全局发育。此外，营养感应枢纽 mTORC1 在这个过程中起着负作用。总之，我们的数据表明，游离脂肪酸作为启动 C. elegans 早期发育的主要营养信号，这表明特定的营养素而不是内在的遗传程序，是胚胎后发育的第一推动力。
