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Extracellular vesicles released from microglia after palmitate exposure impact brain function

De Paula, Gabriela C. LU ; Aldana, Blanca I. ; Battistella, Roberta LU ; Fernández-Calle, Rosalía LU ; Bjure, Andreas ; Lundgaard, Iben LU ; Deierborg, Tomas LU orcid and Duarte, João M.N. LU orcid (2024) In Journal of Neuroinflammation 21(1).
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... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Energy metabolism, Glycolysis, LPS, Neuroinflammation, Obesity
in
Journal of Neuroinflammation
volume
21
issue
1
article number
173
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85198668240
  • pmid:39014461
ISSN
1742-2094
DOI
10.1186/s12974-024-03168-7
language
English
LU publication?
yes
id
4691ffeb-8a4e-4720-a798-ba535c869279
date added to LUP
2024-08-27 15:23:17
date last changed
2025-06-04 17:30:04
@article{4691ffeb-8a4e-4720-a798-ba535c869279,
  abstract     = {{<p>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.</p>}},
  author       = {{De Paula, Gabriela C. and Aldana, Blanca I. and Battistella, Roberta and Fernández-Calle, Rosalía and Bjure, Andreas and Lundgaard, Iben and Deierborg, Tomas and Duarte, João M.N.}},
  issn         = {{1742-2094}},
  keywords     = {{Energy metabolism; Glycolysis; LPS; Neuroinflammation; Obesity}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Journal of Neuroinflammation}},
  title        = {{Extracellular vesicles released from microglia after palmitate exposure impact brain function}},
  url          = {{http://dx.doi.org/10.1186/s12974-024-03168-7}},
  doi          = {{10.1186/s12974-024-03168-7}},
  volume       = {{21}},
  year         = {{2024}},
}