Palmitic Acid-Induced NAD+ Depletion is Associated with the Reduced Function of SIRT1 and Increased Expression of BACE1 in Hippocampal Neurons
Increased levels of circulating fatty acids, such as palmitic acid (PA), are associated with the development of obesity, insulin resistance, type-2 diabetes and metabolic syndrome. Furthermore, these diseases are linked to an increased risk of cancer, cardiovascular diseases, mild cognitive impairment and even Alzheimer’s disease (AD). However, the precise actions of elevated PA levels on neurons and their association with neuronal metabolic disruption that leads to the expression of pathological markers of AD, such as the overproduction and accumulation of the amyloid-β peptide, represent an area of intense investigation. A possible molecular mechanism involved in the effects of PA may be through dysfunction of the NAD+ sensor enzyme, SIRT1. Therefore, the aim of the present study was to analyze the relationship between the effects of PA metabolism on the function of SIRT1 and the upregulation of BACE1 in cultured hippocampal neurons. PA reduced the total amount of NAD+ in neurons that caused an increase in p65 K310 acetylation due to inhibition of SIRT1 activity and low protein content. Furthermore, BACE1 protein and its activity were increased, and BACE1 was relocated in neurites after PA exposure.
KeywordsPalmitic acid SIRT1 BACE1 expression Neuronal NAD+ Hippocampal neurons
This work was supported by Universidad Nacional Autónoma de México (UNAM) (PAPIIT IN202615). The authors thank Patricia Ferrera for technical assistance and Miguel Tapia-Rodriguez for confocal microscopy assistance. M Flores-León is a doctoral student from Programa de Doctorado en Ciencias Bioquímicas, Universidad Nacional Autónoma de México (UNAM) and received a fellowship from CONACYT (449712).
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest.
All procedures involving animals in this studied were performance in accordance with the Regulations for Research in Health Matters (México) and with the approval of the local Animal Care Committee.
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