Extracellular macrophage migration inhibitory factor (MIF) downregulates adipose hormone-sensitive lipase (HSL) and contributes to obesity.
AMP activated protein kinase (AMPK)
Adipose tissue
Hormone-sensitive lipase (HSL)
Macrophage migration inhibitory factor (MIF)
Obesity
c-Jun N-terminal kinase (JNK)
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
05 Nov 2023
05 Nov 2023
Historique:
received:
15
08
2023
revised:
21
10
2023
accepted:
02
11
2023
pubmed:
8
11
2023
medline:
8
11
2023
entrez:
7
11
2023
Statut:
aheadofprint
Résumé
Attenuation of adipose hormone sensitive lipase (HSL) may impair lipolysis and exacerbate obesity. We investigate the role of cytokine, macrophage migration inhibitory factor (MIF) in regulating adipose HSL and adipocyte hypertrophy. Extracellular MIF downregulates HSL in an autocrine fashion, by activating the AMPK/JNK signaling pathway upon binding to its membrane receptor, CD74. WT mice fed high fat diet (HFD), as well as mice overexpressing MIF, both had high circulating MIF levels and showed suppression of HSL during the development of obesity. Blocking the extracellular action of MIF by a neutralizing MIF antibody significantly reduced obesity in HFD mice. Interestingly, intracellular MIF binds with COP9 signalosome subunit 5 (Csn5) and JNK, which leads to an opposing effect to inhibit JNK phosphorylation. With global MIF deletion, adipocyte JNK phosphorylation increased, resulting in decreased HSL expression, suggesting that the loss of MIF's intracellular inhibitory action on JNK was dominant in Mif
Identifiants
pubmed: 37935315
pii: S2212-8778(23)00168-0
doi: 10.1016/j.molmet.2023.101834
pmc: PMC10700858
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
101834Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest All the authors declare that no potential conflicts of interest relevant to this article.
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