Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting.
S-adenosylmethionine
adipose tissue
caloric restriction
endoplasmic reticulum stress
fasting
liver
methionine adenosyltransferase a1
mitochondria-associated-membranes
phosphatidylethanolamine methyltransferase
β-oxidation
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
08 08 2023
08 08 2023
Historique:
received:
27
08
2020
revised:
30
03
2023
accepted:
06
07
2023
medline:
11
8
2023
pubmed:
2
8
2023
entrez:
1
8
2023
Statut:
ppublish
Résumé
There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)-the principal methyl donor-acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues. Notably, we show that glucagon induces the expression of the hepatic SAMe-synthesizing enzyme methionine adenosyltransferase α1 (MAT1A), which translocates to mitochondria-associated membranes. This leads to the production of this metabolite at these sites, which acts as a brake to prevent excessive β-oxidation and mitochondrial ATP synthesis and thereby endoplasmic reticulum stress and liver injury. This work provides important insights into the previously undescribed function of SAMe as a new arm of the metabolic adaptation to fasting.
Identifiants
pubmed: 37527658
pii: S1550-4131(23)00261-9
doi: 10.1016/j.cmet.2023.07.002
pmc: PMC10432853
pii:
doi:
Substances chimiques
S-Adenosylmethionine
7LP2MPO46S
Adenosine Triphosphate
8L70Q75FXE
Methionine Adenosyltransferase
EC 2.5.1.6
PEMT protein, mouse
EC 2.1.1.17
Phosphatidylethanolamine N-Methyltransferase
EC 2.1.1.17
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1373-1389.e8Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests M.L.M.-C. advises for Mitotherapeutix.
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