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
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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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID |
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Ratnappan, R | | | | Amrit, FRG | | | | Chen, SW | | | | Gill, H | | | | Holden, K | | | | Ward, J | | | | Yamamoto, KR | | | | Olsen, CP | | | | Ghazi, A | ghazia@pitt.edu | GHAZIA | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID |
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Editor | Ashrafi, Kaveh | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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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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