Role of adipocyte Na,K-ATPase oxidant amplification loop in cognitive decline and neurodegeneration.
Cell biology
Molecular physiology
Neuroscience
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
19 Nov 2021
19 Nov 2021
Historique:
received:
28
02
2021
revised:
10
08
2021
accepted:
11
10
2021
entrez:
10
11
2021
pubmed:
11
11
2021
medline:
11
11
2021
Statut:
epublish
Résumé
Recent studies suggest that a western diet may contribute to clinical neurodegeneration and dementia. Adipocyte-specific expression of the Na,K-ATPase signaling antagonist, NaKtide, ameliorates the pathophysiological consequences of murine experimental obesity and renal failure. In this study, we found that a western diet produced systemic oxidant stress along with evidence of activation of Na,K-ATPase signaling within both murine brain and peripheral tissues. We also noted this diet caused increases in circulating inflammatory cytokines as well as behavioral, and brain biochemical changes consistent with neurodegeneration. Adipocyte specific NaKtide affected by a doxycycline on/off expression system ameliorated all of these diet effects. These data suggest that a western diet produces cognitive decline and neurodegeneration through augmented Na,K-ATPase signaling and that antagonism of this pathway in adipocytes ameliorates the pathophysiology. If this observation is confirmed in humans, the adipocyte Na,K-ATPase may serve as a clinical target in the therapy of neurodegenerative disorders.
Identifiants
pubmed: 34755095
doi: 10.1016/j.isci.2021.103262
pii: S2589-0042(21)01231-1
pmc: PMC8564125
doi:
Types de publication
Journal Article
Langues
eng
Pagination
103262Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103434
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM121299
Pays : United States
Organisme : NHLBI NIH HHS
ID : R15 HL150721
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM104942
Pays : United States
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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