| RRC ID |
45835
|
| 著者 |
Ratnappan R, Amrit FR, Chen SW, Gill H, Holden K, Ward J, Yamamoto KR, Olsen CP, Ghazi A.
|
| タイトル |
Germline signals deploy NHR-49 to modulate fatty-acid β-oxidation and desaturation in somatic tissues of C. elegans.
|
| ジャーナル |
PLoS Genet
|
| 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.
|
| 巻・号 |
10(12)
|
| ページ |
e1004829
|
| 公開日 |
2014-12-1
|
| DOI |
10.1371/journal.pgen.1004829
|
| PII |
PGENETICS-D-14-01216
|
| PMID |
25474470
|
| PMC |
PMC4256272
|
| MeSH |
Animals
Animals, Genetically Modified
Caenorhabditis elegans* / genetics
Caenorhabditis elegans* / metabolism
Caenorhabditis elegans Proteins / genetics
Caenorhabditis elegans Proteins / metabolism
Caenorhabditis elegans Proteins / physiology*
Fatty Acids / metabolism*
Female
Forkhead Transcription Factors / metabolism
Germ Cells / metabolism*
Lipid Metabolism / genetics*
Longevity / genetics
Oxidation-Reduction
Peptide Elongation Factors / metabolism
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism
Receptors, Cytoplasmic and Nuclear / physiology*
Reproduction / genetics
Signal Transduction / genetics
|
| IF |
5.175
|
| 引用数 |
53
|
|
WOS 分野
|
GENETICS & HEREDITY
|
| リソース情報 |
| 線虫 |
tm1452 |
