Endocrine pheromones couple fat rationing to dauer diapause through HNF4αnuclear receptors  

作　　者：Cheng Gao Qi Li Jialei Yu Shiwei Li Qingpo Cui Xiao Hu Lifeng Chen Shaobing O.Zhang 

机构地区：[1]Laboratory of Metabolic Genetics,College of Life Sciences,Capital Normal University,Beijing 100048,China

出　　处：《Science China(Life Sciences)》2021年第12期2153-2174,共22页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China(91857106 and 31770865);by the CGC,which is funded by NIH Office of Research Infrastructure Programs(P40 OD010440)of USA;by the Mitani Lab through the National Bio-Resource Project of the MEXT of Japan。

摘　　要：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(peroxisomalβ-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 HNF4αfamily 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.

关 键 词：dauer diapause pheromone fatty acidβ-oxidation PEROXISOME nuclear receptor 

分 类 号：Q41[生物学—生理学]