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Updated: Jul 24, 2026
Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
Published on: October 25, 2016
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.
Abstract:
Dietary patterns that include an excess of foods rich in saturated fat are associated with brain dysfunction. Although microgliosis has been proposed to play a key role in the development of brain dysfunction in diet-induced obesity (DIO), neuroinflammation with cytokine over-expression is not always observed. Thus, mechanisms by which microglia contribute to brain impairment in DIO are uncertain. Using the BV2 cell model, we investigated the gliosis profile of microglia exposed to palmitate (200 µmol/L), a saturated fatty acid abundant in high-fat diet and in the brain of obese individuals. We observed that microglia respond to a 24-hour palmitate exposure with increased proliferation, and with a metabolic network rearrangement that favors energy production from glycolysis rather than oxidative metabolism, despite stimulated mitochondria biogenesis. In addition, while palmitate did not induce increased cytokine expression, it modified the protein cargo of released extracellular vesicles (EVs). When administered intra-cerebroventricularly to mice, EVs secreted from palmitate-exposed microglia in vitro led to memory impairment, depression-like behavior, and glucose intolerance, when compared to mice receiving EVs from vehicle-treated microglia. We conclude that microglia exposed to palmitate can mediate brain dysfunction through the cargo of shed EVs.
Insights
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.
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.
