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Germline Signals Deploy NHR-49 to Modulate Fatty-Acid β-Oxidation and Desaturation in Somatic Tissues of C. elegans

Ratnappan, R and Amrit, FRG and Chen, SW and Gill, H and Holden, K and Ward, J and Yamamoto, KR and Olsen, CP and Ghazi, A (2014) Germline Signals Deploy NHR-49 to Modulate Fatty-Acid β-Oxidation and Desaturation in Somatic Tissues of C. elegans. PLoS Genetics, 10 (12). ISSN 1553-7390

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Abstract

In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ratnappan, R
Amrit, FRG
Chen, SW
Gill, H
Holden, K
Ward, J
Yamamoto, KR
Olsen, CP
Ghazi, Aghazia@pitt.eduGHAZIA
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorAshrafi, KavehUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 December 2014
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 10
Number: 12
DOI or Unique Handle: 10.1371/journal.pgen.1004829
Schools and Programs: School of Medicine > Pediatrics
Refereed: Yes
ISSN: 1553-7390
Other ID: NLM PMC4256272
PubMed Central ID: PMC4256272
PubMed ID: 25474470
Date Deposited: 12 May 2015 18:42
Last Modified: 12 Oct 2021 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/24071

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