Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-α
Summary: 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 pal...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-02-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720300978 |
| id |
doaj-a8705f38283e423d9640c717a5d7ee14 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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. Ferreira Fernanda G. De Felice |
| spellingShingle |
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. Ferreira Fernanda G. De Felice Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-α Cell Reports |
| author_facet |
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. Ferreira Fernanda G. De Felice |
| author_sort |
Helen M. Melo |
| title |
Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-α |
| title_short |
Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-α |
| title_full |
Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-α |
| title_fullStr |
Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-α |
| title_full_unstemmed |
Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-α |
| title_sort |
palmitate is increased in the cerebrospinal fluid of humans with obesity and induces memory impairment in mice via pro-inflammatory tnf-α |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2020-02-01 |
| description |
Summary: 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. : Obesity has been associated with cognitive decline. Melo et al. show that palmitate levels are increased in the CSF of overweight and obese humans. In mice, intracerebroventricular infusion of palmitate impairs synaptic plasticity and memory. Microglial-derived TNF-α mediates the deleterious actions of palmitate in the brain. Keywords: palmitate, memory impairment, obesity, brain inflammation, microglia, TNF-α, insulin signaling |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124720300978 |
| work_keys_str_mv |
AT helenmmelo palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT giseledasseixasdasilva palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT marcellaramossantana palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT camilavieiraligoteixeira palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT juliarclarke palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT viviansmiyacoreixas palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT brunocdemelo palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT julianatsfortuna palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT leticiafornygermano palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT josehenriqueledo palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT mairasoliveira palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT claudiapfigueiredo palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT raphaellepardossipiquard palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT fredericchecler palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT josemariadelgadogarcia palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT agnesgruart palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT licioavelloso palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT marciolfbalthazar palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT dennysecintra palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT sergiotferreira palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa AT fernandagdefelice palmitateisincreasedinthecerebrospinalfluidofhumanswithobesityandinducesmemoryimpairmentinmiceviaproinflammatorytnfa |
| _version_ |
1724783470608121856 |
| spelling |
doaj-a8705f38283e423d9640c717a5d7ee142020-11-25T02:40:01ZengElsevierCell Reports2211-12472020-02-0130721802194.e8Palmitate Is Increased in the Cerebrospinal Fluid of Humans with Obesity and Induces Memory Impairment in Mice via Pro-inflammatory TNF-αHelen M. Melo0Gisele da S. Seixas da Silva1Marcella Ramos Sant’Ana2Camila Vieira Ligo Teixeira3Julia R. Clarke4Vivian S. Miya Coreixas5Bruno C. de Melo6Juliana T.S. Fortuna7Leticia Forny-Germano8José Henrique Ledo9Maíra S. Oliveira10Claudia P. Figueiredo11Raphaelle Pardossi-Piquard12Frédéric Checler13José María Delgado-García14Agnès Gruart15Licio A. Velloso16Marcio L.F. Balthazar17Dennys E. Cintra18Sergio T. Ferreira19Fernanda G. De Felice20Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilFederal Institute of Education, Science and Technology of Rio de Janeiro, Rio de Janeiro, RJ 20270-021, BrazilLaboratory of Nutritional Genomics (LabGeN), School of Applied Sciences and CELN - Nutrigenomics and Lipids Research Center, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP 13484-350, BrazilBrazilian Institute of Neuroscience and Neurotechnology (BRAINN) and Department of Neurology, Neuroimaging Laboratory, University of Campinas (UNICAMP), Campinas, SP 13083-887, BrazilSchool of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilSchool of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilUniversité Côte d’Azur, INSERM, CNRS/UMR7275, IPMC, team labeled “Laboratory of Excellence (LABEX) Distalz,” 660 route des Lucioles, 06560 Sophia-Antipolis, Valbonne, FranceUniversité Côte d’Azur, INSERM, CNRS/UMR7275, IPMC, team labeled “Laboratory of Excellence (LABEX) Distalz,” 660 route des Lucioles, 06560 Sophia-Antipolis, Valbonne, FranceDivision of Neuroscience, Pablo de Olavide University, Seville 41013, SpainDivision of Neuroscience, Pablo de Olavide University, Seville 41013, SpainLaboratory of Cell Signalling, Obesity and Comorbidities Research Centre, University of Campinas, Campinas, SP 13084-761, BrazilBrazilian Institute of Neuroscience and Neurotechnology (BRAINN) and Department of Neurology, Neuroimaging Laboratory, University of Campinas (UNICAMP), Campinas, SP 13083-887, BrazilLaboratory of Nutritional Genomics (LabGeN), School of Applied Sciences and CELN - Nutrigenomics and Lipids Research Center, School of Applied Sciences, University of Campinas (UNICAMP), Limeira, SP 13484-350, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil; Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, BrazilInstitute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil; Centre for Neuroscience Studies and Department of Psychiatry, Queen’s University, Kingston, ON K7L 3N6, Canada; Corresponding authorSummary: 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. : Obesity has been associated with cognitive decline. Melo et al. show that palmitate levels are increased in the CSF of overweight and obese humans. In mice, intracerebroventricular infusion of palmitate impairs synaptic plasticity and memory. Microglial-derived TNF-α mediates the deleterious actions of palmitate in the brain. Keywords: palmitate, memory impairment, obesity, brain inflammation, microglia, TNF-α, insulin signalinghttp://www.sciencedirect.com/science/article/pii/S2211124720300978 |