Polyunsaturated fatty acids and p38-MAPK link metabolic reprogramming to cytoprotective gene expression during dietary restriction.
Animals
Biochemical Phenomena
Caenorhabditis elegans
/ genetics
Caenorhabditis elegans Proteins
/ genetics
Eicosapentaenoic Acid
/ analogs & derivatives
Fatty Acids, Unsaturated
/ genetics
Gene Expression Regulation
/ genetics
Gene Knockdown Techniques
Linoleic Acid
/ metabolism
Longevity
Metabolic Networks and Pathways
/ genetics
Protein Serine-Threonine Kinases
/ genetics
p38 Mitogen-Activated Protein Kinases
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
25 09 2020
25 09 2020
Historique:
received:
27
08
2019
accepted:
02
09
2020
entrez:
26
9
2020
pubmed:
27
9
2020
medline:
21
10
2020
Statut:
epublish
Résumé
The metabolic state of an organism instructs gene expression modalities, leading to changes in complex life history traits, such as longevity. Dietary restriction (DR), which positively affects health and life span across species, leads to metabolic reprogramming that enhances utilisation of fatty acids for energy generation. One direct consequence of this metabolic shift is the upregulation of cytoprotective (CyTP) genes categorized in the Gene Ontology (GO) term of "Xenobiotic Detoxification Program" (XDP). How an organism senses metabolic changes during nutritional stress to alter gene expression programs is less known. Here, using a genetic model of DR, we show that the levels of polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) and eicosapentaenoic acid (EPA), are increased following DR and these PUFAs are able to activate the CyTP genes. This activation of CyTP genes is mediated by the conserved p38 mitogen-activated protein kinase (p38-MAPK) pathway. Consequently, genes of the PUFA biosynthesis and p38-MAPK pathway are required for multiple paradigms of DR-mediated longevity, suggesting conservation of mechanism. Thus, our study shows that PUFAs and p38-MAPK pathway function downstream of DR to help communicate the metabolic state of an organism to regulate expression of CyTP genes, ensuring extended life span.
Identifiants
pubmed: 32978396
doi: 10.1038/s41467-020-18690-4
pii: 10.1038/s41467-020-18690-4
pmc: PMC7519657
doi:
Substances chimiques
Caenorhabditis elegans Proteins
0
Fatty Acids, Unsaturated
0
eicosapentaenoic acid ethyl ester
6GC8A4PAYH
Linoleic Acid
9KJL21T0QJ
Eicosapentaenoic Acid
AAN7QOV9EA
Protein Serine-Threonine Kinases
EC 2.7.11.1
drl-1 protein, C elegans
EC 2.7.11.1
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
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
4865Subventions
Organisme : NIH HHS
ID : P40 OD010440
Pays : United States
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