The Saturated Fatty Acid Palmitate Induces Human Monocytic Cell Toxicity Toward Neuronal Cells: Exploring a Possible Link Between Obesity-Related Metabolic Impairments and Neuroinflammation

Issue title: Metabolic-Cognitive Syndrome: Update on the Metabolic Pathway in Neurodegenerative Disorders

Guest editors: Vincenza Frisardi and Bruno Imbimbo

Article type: Research Article

Authors: Little, Jonathan P.^{; *} | Madeira, Jocelyn M. | Klegeris, Andis

Affiliations: Department of Biology, I.K. Barber School of Arts and Sciences, University of British Columbia Okanagan, Kelowna, BC, Canada

Correspondence: [*] Correspondence to: Jonathan Little, PhD, Department of Biology, 3333 University Way, Kelowna, BC V1V 1V7, Canada. Tel.: +1 250 878 6893; Fax: +1 250 807 8005; E-mail: jonathan.little@ubc.ca.

Abstract: Obesity is linked to increased risk of Alzheimer's disease and cognitive impairment. Microglia-mediated neuroinflammation is implicated in neuronal loss. Elevated levels of fatty acids seen in obesity induce inflammation in peripheral tissues. Whether fatty acids promote neuroinflammation is unknown. Using an established neuroinflammation model involving human microglia-like THP-1 cells and SH-SY5Y neuroblastoma cells, we show that the saturated fatty acid palmitate, but not the unsaturated fatty acids oleate or linoleate, induces THP-1 cell pro-inflammatory cytokine secretion and neurotoxicity. Inhibition of c-Jun NH2-terminal kinase (JNK) reduces this neurotoxicity. Therefore, elevated saturated fatty acids may induce neuroinflammation through pathways involving JNK activation.

Keywords: Alzheimer's disease, metabolic syndrome X, microglia, neurodegeneration, palmitic acid

DOI: 10.3233/JAD-2011-111262

Journal: Journal of Alzheimer's Disease, vol. 30, no. s2, pp. S179-S183, 2012