Palmitic acid induces insulin resistance by a mechanism associated with energy metabolism and calcium entry in neuronal cells.
Palmitic acid (PA) is a saturated fatty acid whose high consumption has been largely associated with the development of different metabolic alterations, such as insulin resistance, metabolic syndrome, and type 2 diabetes. Particularly in the brain, insulin signaling disruption has been linked to cognitive decline and is considered a risk factor for Alzheimer's disease. Cumulative evidence has demonstrated the participation of PA in the molecular cascade underlying cellular insulin resistance in peripheral tissues, but its role in the development of neuronal insulin resistance and the mechanisms involved are not fully understood. It has generally been accepted that the brain does not utilize fatty acids as a primary energy source, but recent evidence shows that neurons possess the machinery for fatty acid β-oxidation. However, it is still unclear under what conditions neurons use fatty acids as energy substrates and the implications of their oxidative metabolism in modifying insulin-stimulated effects. In the present work, we have found that neurons differentiated from human neuroblastoma MSN exposed to high but nontoxic concentrations of PA generate ATP through mitochondrial metabolism, which is associated with an increase in the cytosolic Ca2+ and diminished insulin signaling in neurons. These findings reveal a novel mechanism by which saturated fatty acids produce Ca2+ entry and insulin resistance that may play a causal role in increasing neuronal vulnerability associated with metabolic diseases.
['Sánchez-Alegría|Karina|K|', 'Bastián-Eugenio|Carlos Ernesto|CE|', 'Vaca|Luis|L|', 'Arias|Clorinda|C|']
D000255:Adenosine Triphosphate D002118:Calcium D045744:Cell Line, Tumor D003600:Cytosol D004734:Energy Metabolism D005227:Fatty Acids D006801:Humans D007328:Insulin D007333:Insulin Resistance D008928:Mitochondria D009447:Neuroblastoma D009474:Neurons D019308:Palmitic Acid D015398:Signal Transduction
palmitic acid neuronal insulin resistance PKC activation intraneuronal Ca2+ neuronal β-oxidation