Palmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro

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dc.contributor.authorEspinosa, Rodrigo
dc.contributor.authorGutierrez, Karla
dc.contributor.authorRios, Javiera
dc.contributor.authorOrmeno, Fernando
dc.contributor.authorYanten, Liliana
dc.contributor.authorGalaz-Davison, Pablo
dc.contributor.authorRamirez-Sarmiento, Cesar A.
dc.contributor.authorParra, Valentina
dc.contributor.authorAlbornoz, Amelina
dc.contributor.authorAlfaro, Ivan E.
dc.contributor.authorBurgos, Patricia, V
dc.contributor.authorMorselli, Eugenia
dc.contributor.authorCriollo, Alfredo
dc.contributor.authorBudini, Mauricio
dc.date.accessioned2025-01-20T21:10:13Z
dc.date.available2025-01-20T21:10:13Z
dc.date.issued2022
dc.description.abstractThe intake of food with high levels of saturated fatty acids (SatFAs) is associated with the development of obesity and insulin resistance. SatFAs, such as palmitic (PA) and stearic (SA) acids, have been shown to accumulate in the hypothalamus, causing several pathological consequences. Autophagy is a lysosomal-degrading pathway that can be divided into macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Previous studies showed that PA impairs macroautophagy function and insulin response in hypothalamic proopiomelanocortin (POMC) neurons. Here, we show in vitro that the exposure of POMC neurons to PA or SA also inhibits CMA, possibly by decreasing the total and lysosomal LAMP2A protein levels. Proteomics of lysosomes from PA- and SA-treated cells showed that the inhibition of CMA could impact vesicle formation and trafficking, mitochondrial components, and insulin response, among others. Finally, we show that CMA activity is important for regulating the insulin response in POMC hypothalamic neurons. These in vitro results demonstrate that CMA is inhibited by PA and SA in POMC-like neurons, giving an overview of the CMA-dependent cellular pathways that could be affected by such inhibition and opening a door for in vivo studies of CMA in the context of the hypothalamus and obesity.
dc.fuente.origenWOS
dc.identifier.doi10.3390/cells11060920
dc.identifier.eissn2073-4409
dc.identifier.urihttps://doi.org/10.3390/cells11060920
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/93569
dc.identifier.wosidWOS:000775778500001
dc.issue.numero6
dc.language.isoen
dc.revistaCells
dc.rightsacceso restringido
dc.subjectchaperone-mediated autophagy (CMA)
dc.subjectinsulin
dc.subjectpalmitic
dc.subjectstearic
dc.subjectlysosome
dc.subjectobesity
dc.subjectproteomics
dc.subjectSILAC
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePalmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro
dc.typeartículo
dc.volumen11
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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