| Title: | Endocrine pheromones couple fat rationing to dauer diapause through HNF4alpha nuclear receptors |
| Author(s): | Gao C; Li Q; Yu J; Li S; Cui Q; Hu X; Chen L; Zhang SO; |
| Address: | "Laboratory of Metabolic Genetics, College of Life Sciences, Capital Normal University, Beijing, 100048, China. Laboratory of Metabolic Genetics, College of Life Sciences, Capital Normal University, Beijing, 100048, China. soz001@cnu.edu.cn" |
| DOI: | 10.1007/s11427-021-2016-9 |
| ISSN/ISBN: | 1869-1889 (Electronic) 1674-7305 (Linking) |
| Abstract: | "Developmental diapause is a widespread strategy for animals to survive seasonal starvation and environmental harshness. Diapaused animals often ration body fat to generate a basal level of energy for enduring survival. How diapause and fat rationing are coupled, however, is poorly understood. The nematode Caenorhabditis elegans excretes pheromones to the environment to induce a diapause form called dauer larva. Through saturated forward genetic screens and CRISPR knockout, we found that dauer pheromones feed back to repress the transcription of ACOX-3, MAOC-1, DHS-28, DAF-22 (peroxisomal beta-oxidation enzymes dually involved in pheromone synthesis and fat burning), ALH-4 (aldehyde dehydrogenase for pheromone synthesis), PRX-10 and PRX-11 (peroxisome assembly and proliferation factors). Dysfunction of these pheromone enzymes and factors relieves the repression. Surprisingly, transcription is repressed not by pheromones excreted but by pheromones endogenous to each animal. The endogenous pheromones regulate the nuclear translocation of HNF4alpha family nuclear receptor NHR-79 and its co-receptor NHR-49, and, repress transcription through the two receptors. The feedback repression maintains pheromone homeostasis, increases fat storage, decreases fat burning, and prolongs dauer lifespan. Thus, the exocrine dauer pheromones possess an unexpected endocrine function to mediate a peroxisome-nucleus crosstalk, coupling dauer diapause to fat rationing" |
| Keywords: | Acyl-CoA Oxidase/*metabolism Adipose Tissue/metabolism Animals Caenorhabditis elegans/genetics/*metabolism Diapause/physiology Fatty Acids/*metabolism Hepatocyte Nuclear Factor 4/*metabolism Homeostasis/physiology Larva Oxidation-Reduction Peroxisomes/met; |
| Notes: | "MedlineGao, Cheng Li, Qi Yu, Jialei Li, Shiwei Cui, Qingpo Hu, Xiao Chen, Lifeng Zhang, Shaobing O eng China 2021/11/11 Sci China Life Sci. 2021 Dec; 64(12):2153-2174. doi: 10.1007/s11427-021-2016-9. Epub 2021 Nov 5" |
