Extracellular vesicles released from microglia after palmitate exposure impact brain function
(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
- De Paula, Gabriela C.
LU
; Aldana, Blanca I.
; Battistella, Roberta
LU
; Fernández-Calle, Rosalía
LU
; Bjure, Andreas
; Lundgaard, Iben
LU
; Deierborg, Tomas
LU
and Duarte, João M.N.
LU
- organization
-
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Diabetes and Brain Function (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- WCMM-Wallenberg Centre for Molecular Medicine
- Glia-Immune Interactions (research group)
- Neuroinflammation (research group)
- LU Profile Area: Proactive Ageing
- Department of Experimental Medical Science
- publishing date
- 2024-12
- 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
-
- pmid:39014461
- scopus:85198668240
- 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
- 2024-08-28 03:00:05
@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}}, }