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Extracellular vesicles released from microglia after palmitate exposure impact brain function.

Gabriela C De Paula1,2, Blanca I Aldana3, Roberta Battistella1,2

  • 1Department of Experimental Medical Science (EMV), Faculty of Medicine, Lund University, Sölvegatan 19, BMC C11, Lund, 221 84, Sweden.

Journal of Neuroinflammation
|July 16, 2024
PubMed
Summary
This summary is machine-generated.

High-fat diets can impair brain function. Microglia exposed to palmitate, a saturated fat, release extracellular vesicles that cause memory loss and behavioral changes in mice.

Keywords:
Energy metabolismGlycolysisLPSNeuroinflammationObesity

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Metabolism

Background:

  • Dietary patterns high in saturated fat are linked to brain dysfunction.
  • Microglia are implicated in diet-induced obesity (DIO) brain dysfunction, but mechanisms remain unclear.
  • Neuroinflammation and cytokine over-expression are not consistently observed in DIO.

Purpose of the Study:

  • To investigate the gliosis profile of microglia exposed to palmitate, a saturated fatty acid.
  • To understand how palmitate affects microglial metabolism and extracellular vesicle (EV) release.
  • To determine if EVs from palmitate-exposed microglia can induce brain dysfunction.

Main Methods:

  • BV2 microglial cells were exposed to palmitate (200 µmol/L).
  • Microglial proliferation, metabolism, and EV protein cargo were analyzed.
  • EVs from palmitate-exposed microglia were administered intra-cerebroventricularly to mice.

Main Results:

  • Palmitate exposure increased microglial proliferation and shifted metabolism towards glycolysis.
  • Mitochondrial biogenesis was stimulated, but oxidative metabolism was not favored.
  • Palmitate-exposed microglia released EVs with altered protein cargo.
  • EVs from palmitate-exposed microglia induced memory impairment, depression-like behavior, and glucose intolerance in mice.

Conclusions:

  • Microglia respond to palmitate by altering their metabolism and EV cargo.
  • Microglia can mediate brain dysfunction in DIO through the release of specific EVs.
  • EVs from palmitate-exposed microglia represent a potential mechanism for saturated fat-induced brain impairment.