Cited by 143Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-α

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Melo, Helen M., Seixas da Silva, Gisele da S., Sant’Ana, Marcella Ramos, Teixeira, Camila Vieira Ligo, Clarke, Julia R., Miya Coreixas, Vivian S., de Melo, Bruno C., Fortuna, Juliana T.S. +13 more·2020·Cell Reports

Abstract

Obesity has been associated with cognitive decline, atrophy of brain regions related to learning and memory, and higher risk of developing dementia. However, the molecular mechanisms underlying these neurological alterations are still largely unknown. Here, we investigate the effects of palmitate, a saturated fatty acid present at high amounts in fat-rich diets, in the brain. Palmitate is increased in the cerebrospinal fluid (CSF) of overweight and obese patients with amnestic mild cognitive impairment. In mice, intracerebroventricular infusion of palmitate impairs synaptic plasticity and memory. Palmitate induces astroglial and microglial activation in the mouse hippocampus, and its deleterious impact is mediated by microglia-derived tumor necrosis factor alpha (TNF-α) signaling. Our results establish that obesity is associated with increases in CSF palmitate. By defining a pro-inflammatory mechanism by which abnormal levels of palmitate in the brain impair memory, the results further suggest that anti-inflammatory strategies may attenuate memory impairment in obesity.

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Crossref · 10.1016/j.celrep.2020.01.072

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Authors
Melo, H. M., Seixas da Silva, G. D. S., Sant’Ana, M. R., Teixeira, C. V. L., Clarke, J. R., Miya Coreixas, V. S., de Melo, B. C., Fortuna, J. T. S., Forny-Germano, L., Ledo, J. H., Oliveira, M. S., Figueiredo, C. P., Pardossi-Piquard, R., Checler, F., Delgado-García, J. M., Gruart, A., Velloso, L. A., Balthazar, M. L. F., Cintra, D. E., Ferreira, S. T., & De Felice, F. G.
Affiliations
  • Universidade Federal do Rio de Janeiro (BR)
  • Universidade Estadual de Campinas (UNICAMP) (BR)
  • Centre National de la Recherche Scientifique (FR)
  • Universidad Pablo de Olavide (ES)
Venue
Cell Reports
Publisher
Elsevier BV
Published
2020-02
Volume
30
Issue
7
Pages
2180-2194.e8
ISSN
2211-1247 (ISSN-L)
OpenAlex
W3007137838
Cited by
140
References
90
Citations by year
2026: 12 · 2025: 17 · 2024: 26 · 2023: 22 · 2022: 28 · 2021: 26 · 2020: 8
FWCI
8.13
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Institute for Translational Neuroscience
  • Human Frontier Science Program
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Labex
  • Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
  • John Simon Guggenheim Memorial Foundation
  • Universidade Federal do Rio de Janeiro
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
palmitate, obesity, cerebrospinal fluid, memory impairment, TNF-α, neuroinflammation, microglial activation, astroglial activation, hippocampus, synaptic plasticity, amnestic mild cognitive impairment, intracerebroventricular infusion, anti-inflammatory therapy
MeSH terms
Animals, Humans, Memory Disorders, Obesity, Palmitates, Tumor Necrosis Factor-alpha, Mice

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