eprintid: 28519 rev_number: 27 userid: 5901 dir: disk0/00/02/85/19 datestamp: 2016-08-23 13:41:09 lastmod: 2021-04-11 08:55:03 status_changed: 2016-08-23 13:41:09 type: article metadata_visibility: show item_issues_count: 0 eprint_status: archive creators_name: Amrit, FRG creators_name: Steenkiste, EM creators_name: Ratnappan, R creators_name: Chen, SW creators_name: McClendon, TB creators_name: Kostka, D creators_name: Yanowitz, J creators_name: Olsen, CP creators_name: Ghazi, A creators_email: creators_email: creators_email: creators_email: creators_email: TBM20@pitt.edu creators_email: kostka@pitt.edu creators_email: creators_email: creators_email: ghazia@pitt.edu creators_id: creators_id: creators_id: creators_id: creators_id: TBM20 creators_id: KOSTKA creators_id: creators_id: creators_id: GHAZIA contributors_type: http://www.loc.gov/loc.terms/relators/EDT contributors_name: Ashrafi, Kaveh title: DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans ispublished: pub divisions: sch_med_Computational_Systems_Biology divisions: sch_med_Developmental_Biology divisions: sch_med_Obstetrics_Gynecology_Reproductive_Sciences divisions: sch_med_Pediatrics full_text_status: public abstract: Elimination of the proliferating germline extends lifespan in C. elegans. This phenomenon provides a unique platform to understand how complex metazoans retain metabolic homeostasis when challenged with major physiological perturbations. Here, we demonstrate that two conserved transcription regulators essential for the longevity of germline-less adults, DAF-16/FOXO3A and TCER-1/TCERG1, concurrently enhance the expression of multiple genes involved in lipid synthesis and breakdown, and that both gene classes promote longevity. Lipidomic analyses revealed that key lipogenic processes, including de novo fatty acid synthesis, triglyceride production, desaturation and elongation, are augmented upon germline removal. Our data suggest that lipid anabolic and catabolic pathways are coordinately augmented in response to germline loss, and this metabolic shift helps preserve lipid homeostasis. DAF-16 and TCER-1 also perform essential inhibitory functions in germline-ablated animals. TCER-1 inhibits the somatic gene-expression program that facilitates reproduction and represses anti-longevity genes, whereas DAF-16 impedes ribosome biogenesis. Additionally, we discovered that TCER-1 is critical for optimal fertility in normal adults, suggesting that the protein acts as a switch supporting reproductive fitness or longevity depending on the presence or absence of the germline. Collectively, our data offer insights into how organisms adapt to changes in reproductive status, by utilizing the activating and repressive functions of transcription factors and coordinating fat production and degradation. date: 2016-02-01 date_type: published publication: PLoS Genetics volume: 12 number: 2 institution: University of Pittsburgh refereed: TRUE issn: 1553-7390 centers: cen_other_mageewomensresearchinst etd_access_restriction: immediate etd_patent_pending: FALSE id_number: 10.1371/journal.pgen.1005788 citation: Amrit, FRG and Steenkiste, EM and Ratnappan, R and Chen, SW and McClendon, TB and Kostka, D and Yanowitz, J and Olsen, CP and Ghazi, A (2016) DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans. PLoS Genetics, 12 (2). ISSN 1553-7390 document_url: http://d-scholarship-dev.library.pitt.edu/28519/1/journal.pgen.1005788.PDF document_url: http://d-scholarship-dev.library.pitt.edu/28519/3/licence.txt