TY - JOUR

T1 - Transcriptional Profiles Reveal Deregulation of Lipid Metabolism and Inflammatory Pathways in Neurons Exposed to Palmitic Acid

AU - Flores-León, M.

AU - Alcaraz, N.

AU - Pérez-Domínguez, M.

AU - Torres-Arciga, K.

AU - Rebollar-Vega, R.

AU - De la Rosa-Velázquez, I. A.

AU - Arriaga-Canon, C.

AU - Herrera, L. A.

AU - Arias, Clorinda

AU - González-Barrios, Rodrigo

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Palmitic acid

KW - RNAseq

KW - Hippocampal neurons

KW - Neuroinflammation

KW - Lipid metabolism

KW - ALZHEIMER-DISEASE

KW - ACTIVATION

KW - ALPHA

KW - HIPPOCAMPUS

KW - IL-17

KW - SET

U2 - 10.1007/s12035-021-02434-6

DO - 10.1007/s12035-021-02434-6

M3 - Journal article

C2 - 34155583

VL - 58

SP - 4639

EP - 4651

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 9

ER -