Transcriptional Profiles Reveal Deregulation of Lipid Metabolism and Inflammatory Pathways in Neurons Exposed to Palmitic Acid

Molecular Neurobiology - Tập 58 - Trang 4639-4651 - 2021
M. Flores-León1, N. Alcaraz2,3, M. Pérez-Domínguez1, K. Torres-Arciga4, R. Rebollar-Vega5, I. A. De la Rosa-Velázquez5,6, C. Arriaga-Canon4, L. A. Herrera3,4, Clorinda Arias1, Rodrigo González-Barrios4
1Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México
2The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen N, Denmark
3Instituto Nacional de Medicina Genómica, Mexico city, Mexico
4Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico
5Genomics Laboratory, Red de Apoyo a La Investigación - CIC, Universidad Nacional Autónoma de México, INMCNSZ, Mexico City, Mexico
6Next Generation Sequencing Core Facility, Helmholtz Zentrum Muenchen, Neuherberg, Germany

Tóm tắt

The effects of the consumption of high-fat diets (HFD) have been studied to unravel the molecular pathways they are altering in order to understand the link between increased caloric intake, metabolic diseases, and the risk of cognitive dysfunction. The saturated fatty acid, palmitic acid (PA), is the main component of HFD and it has been found increased in the circulation of obese and diabetic people. In the central nervous system, PA has been associated with inflammatory responses in astrocytes, but the effects on neurons exposed to it have not been largely investigated. Given that PA affects a variety of metabolic pathways, we aimed to analyze the transcriptomic profile activated by this fatty acid to shed light on the mechanisms of neuronal dysfunction. In the current study, we profiled the transcriptome response after PA exposition at non-toxic doses in primary hippocampal neurons. Gene ontology and Reactome pathway analysis revealed a pattern of gene expression which is associated with inflammatory pathways, and importantly, with the activation of lipid metabolism that is considered not very active in neurons. Validation by quantitative RT-PCR (qRT-PCR) of Hmgcs2, Angptl4, Ugt8, and Rnf145 support the results obtained by RNAseq. Overall, these findings suggest that neurons are able to respond to saturated fatty acids changing the expression pattern of genes associated with inflammatory response and lipid utilization that may be involved in the neuronal damage associated with metabolic diseases.

Tài liệu tham khảo

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