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

Publication date: 18 February 2020Source: Cell Reports, Volume 30, Issue 7Author(s): Helen M. Melo, Gisele da S. Seixas da Silva, Marcella Ramos Sant’Ana, Camila Vieira Ligo Teixeira, Julia R. Clarke, Vivian S. Miya Coreixas, Bruno C. de Melo, Juliana T.S. Fortuna, Leticia Forny-Germano, José Henrique Ledo, Maíra S. Oliveira, Claudia P. Figueiredo, Raphaelle Pardossi-Piquard, Frédéric Checler, José María Delgado-García, Agnès Gruart, Licio A. Velloso, Marcio L.F. Balthazar, Dennys E. Cintra, Sergio T. FerreiraSummaryObesity 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 i...
Source: Cell Reports - Category: Cytology Source Type: research