Transcriptional Profiles Reveal Deregulation of Lipid Metabolism and Inflammatory Pathways in Neurons Exposed to Palmitic Acid.
M Flores-LeónN AlcarazM Pérez-DomínguezK Torres-ArcigaR Rebollar-VegaI A De la Rosa-VelázquezC Arriaga-CanonL A HerreraClorinda AriasRodrigo González-BarriosPublished in: Molecular neurobiology (2021)
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.
Keyphrases
- fatty acid
- gene expression
- spinal cord
- single cell
- inflammatory response
- oxidative stress
- genome wide
- type diabetes
- high fat diet
- weight loss
- rna seq
- dna methylation
- metabolic syndrome
- adipose tissue
- cerebral ischemia
- mass spectrometry
- wound healing
- subarachnoid hemorrhage
- binding protein
- atomic force microscopy
- dna damage response
- heat shock protein