The ketone body β-hydroxybutyrate shifts microglial metabolism and suppresses amyloid-β oligomer-induced inflammation in human microglia.
Alzheimer's
amyloid
inflammation
ketone
microglia
mitochondria
phagocytosis
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
revised:
15
09
2023
received:
21
06
2023
accepted:
03
10
2023
medline:
26
10
2023
pubmed:
25
10
2023
entrez:
25
10
2023
Statut:
ppublish
Résumé
Fatty acids are metabolized by β-oxidation within the "mitochondrial ketogenic pathway" (MKP) to generate β-hydroxybutyrate (BHB), a ketone body. BHB can be generated by most cells but largely by hepatocytes following exercise, fasting, or ketogenic diet consumption. BHB has been shown to modulate systemic and brain inflammation; however, its direct effects on microglia have been little studied. We investigated the impact of BHB on Aβ oligomer (AβO)-stimulated human iPS-derived microglia (hiMG), a model relevant to the pathogenesis of Alzheimer's disease (AD). HiMG responded to AβO with proinflammatory activation, which was mitigated by BHB at physiological concentrations of 0.1-2 mM. AβO stimulated glycolytic transcripts, suppressed genes in the β-oxidation pathway, and induced over-expression of AD-relevant p46Shc, an endogenous inhibitor of thiolase, actions that are expected to suppress MKP. AβO also triggered mitochondrial Ca
Identifiants
pubmed: 37878335
doi: 10.1096/fj.202301254R
doi:
Substances chimiques
3-Hydroxybutyric Acid
TZP1275679
Amyloid beta-Peptides
0
Ketone Bodies
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23261Subventions
Organisme : NICHD NIH HHS
ID : P50 HD103526
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG025532
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG071665
Pays : United States
Informations de copyright
© 2023 Federation of American Societies for Experimental Biology.
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