The ketone body β-hydroxybutyrate shifts microglial metabolism and suppresses amyloid-β oligomer-induced inflammation in human microglia.
Level 5 - mechanism / opinion, no new human data
In vitro laboratory study using human cell lines without direct clinical patient data
PubMed 37878335 · doi:10.1096/fj.202301254R
What was done
The authors investigated the direct effects of the ketone body β-hydroxybutyrate (BHB, tested at 0.1–2 mM) on human induced pluripotent stem cell-derived microglia (hiMG) exposed to amyloid-β oligomers (AβO), an in vitro model relevant to Alzheimer's disease. They evaluated gene expression related to glycolysis and β-oxidation/ketogenesis, mitochondrial markers (calcium, reactive oxygen species, and permeability transition pore activation), inflammasome activation, and phagocytic activity.
What was found
AβO exposure induced proinflammatory activation, increased glycolytic transcripts, suppressed β-oxidation pathway genes, upregulated p46Shc, elevated mitochondrial Ca2+, increased mitochondrial reactive oxygen species, and activated the mitochondrial permeability transition pore in hiMG. BHB at physiological concentrations (0.1–2 mM) ameliorated these mitochondrial changes, restored the mitochondrial ketogenic pathway, reduced inflammasome activation, and restored phagocytic function impaired by AβO. No exact numbers or statistical values were reported in the abstract.
Why it matters
This study provides cellular mechanistic evidence that β-hydroxybutyrate directly alters human microglial immunometabolism, dampens amyloid-induced neuroinflammation, and rescues impaired phagocytosis.
Limits
This is strictly an in vitro study using stem-cell-derived cell cultures without direct in vivo or clinical human measurements. The abstract provides no specific quantitative effect sizes, replicates, or statistical test values.
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