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