1. Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-α.
- Author
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Melo HM, Seixas da Silva GDS, Sant'Ana MR, Teixeira CVL, Clarke JR, Miya Coreixas VS, de Melo BC, Fortuna JTS, Forny-Germano L, Ledo JH, Oliveira MS, Figueiredo CP, Pardossi-Piquard R, Checler F, Delgado-García JM, Gruart A, Velloso LA, Balthazar MLF, Cintra DE, Ferreira ST, and De Felice FG
- Subjects
- Animals, Humans, Memory Disorders pathology, Mice, Obesity pathology, Memory Disorders etiology, Obesity cerebrospinal fluid, Palmitates cerebrospinal fluid, Tumor Necrosis Factor-alpha metabolism
- 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., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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