title: Germline signals deploy NHR-49 to modulate fatty-acid β-oxidation and desaturation in somatic tissues of C. elegans.
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.
authors.affiliation: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Ratnappan
authors.affiliation: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Francis R G
authors.initials: FR
authors.lastname: Amrit
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Shaw-Wen
authors.initials: SW
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Hasreet
authors.initials: H
authors.lastname: Gill
authors.affiliation: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Kyle
authors.initials: K
authors.lastname: Holden
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Jordan
authors.initials: J
authors.lastname: Ward
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Yamamoto
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Carissa P
authors.initials: CP
authors.lastname: Olsen
authors.affiliation: Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Arjumand
authors.initials: A
authors.lastname: Ghazi
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005854:Germ Cells / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics*; D008136:Longevity / Q000235:genetics; D010084:Oxidation-Reduction; D010445:Peptide Elongation Factors / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012098:Reproduction / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; D051858:Forkhead Transcription Factors; C505159:NHR-49 protein, C elegans; D010445:Peptide Elongation Factors; D018160:Receptors, Cytoplasmic and Nuclear; C108831:daf-16 protein, C elegans; C580768:TCER-1 protein, C elegans