ATGL-1 mediates the effect of dietary restriction and the insulin/IGF-1 signaling pathway on longevity in C. elegans.


Journal

Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730

Informations de publication

Date de publication:
09 2019
Historique:
received: 20 05 2019
revised: 28 06 2019
accepted: 02 07 2019
pubmed: 18 7 2019
medline: 14 4 2020
entrez: 18 7 2019
Statut: ppublish

Résumé

Animal lifespan is controlled through genetic pathways that are conserved from nematodes to humans. Lifespan-promoting conditions in nematodes include fasting and a reduction of insulin/IGF signaling. Here we aimed to investigate the input of the Caenorhabditis elegans homologue of the mammalian rate-limiting lipolytic enzyme Adipose Triglyceride Lipase, ATGL-1, in longevity control. We used a combination of genetic and biochemical approaches to determine the role of ATGL-1 in accumulation of triglycerides and regulation of longevity. We found that expression of ATGL is increased in the insulin receptor homologue mutant daf-2 in a FoxO/DAF-16-dependent manner. ATGL-1 is also up-regulated by fasting and in the eat-2 loss-of-function mutant strain. Overexpression of ATGL-1 increases basal and maximal oxygen consumption rate and extends lifespan in C. elegans. Reduction of ATGL-1 function suppresses longevity of the long-lived mutants eat-2 and daf-2. Our results demonstrate that ATGL is required for extended lifespan downstream of both dietary restriction and reduced insulin/IGF signaling.

Identifiants

pubmed: 31311719
pii: S2212-8778(19)30482-X
doi: 10.1016/j.molmet.2019.07.001
pmc: PMC6717769
pii:
doi:

Substances chimiques

Caenorhabditis elegans Proteins 0
Insulin 0
Insulin-Like Growth Factor I 67763-96-6
ATGL-1 protein, C elegans EC 3.1.1.3
Lipase EC 3.1.1.3

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

75-82

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR001430
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK046200
Pays : United States
Organisme : NIH HHS
ID : P40 OD010440
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK052057
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK052057
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK107498
Pays : United States

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.

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Auteurs

Nava Zaarur (N)

Department of Biochemistry, Boston University School of Medicine, Boston, MA, 02118, USA.

Kathleen Desevin (K)

Department of Biochemistry, Boston University School of Medicine, Boston, MA, 02118, USA.

James Mackenzie (J)

Department of Biochemistry, Boston University School of Medicine, Boston, MA, 02118, USA.

Avery Lord (A)

Department of Biochemistry, Boston University School of Medicine, Boston, MA, 02118, USA.

Alla Grishok (A)

Department of Biochemistry, Boston University School of Medicine, Boston, MA, 02118, USA. Electronic address: agrishok@bu.edu.

Konstantin V Kandror (KV)

Department of Biochemistry, Boston University School of Medicine, Boston, MA, 02118, USA. Electronic address: kkandror@bu.edu.

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Classifications MeSH