Palmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro
Journal
Cells
ISSN
2073-4409
Date Issued
2022
Author(s)
Rodrigo Espinosa
Karla Gutiérrez
Javiera Rios
Fernando Ormeño
Liliana Yantén
Pablo Galaz-Davison
César A. Ramírez-Sarmiento
Valentina Parra
Amelina Albornoz
Patricia V. Burgos
Eugenia Morselli
Alfredo Criollo
Mauricio Budini
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>The 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.</jats:p>
Cite this document
Espinosa, R., Gutiérrez, K., Rios, J., Ormeño, F., Yantén, L., Galaz-Davison, P., Ramírez-Sarmiento, C. A., Parra, V., Albornoz, A., Alfaro, I. E., Burgos, P. V., Morselli, E., Criollo, A., & Budini, M. (2022). Palmitic and stearic acids inhibit chaperone-mediated autophagy (Cma) in pomc-like neurons in vitro. Cells, 11(6), 920. https://doi.org/10.3390/cells11060920
Subjects
chaperone-mediated autophagy (cma)
;
insulin
;
palmitic
;
stearic
;
lysosome
;
obesity
;
proteomics
;
silac
;
chaperone-mediated autophagy
;
humans
;
insulin
;
neurons
;
obesity
;
pro-opiomelanocortin
;
stearic acids
;
13d3
;
4866s
;
9091s
;
9272
;
ab18528
;
glucose 6 phosphate dehydrogenase
;
heat shock cognate protein 70
;
insulin
;
lysosome associated membrane protein 1
;
lysosome associated membrane protein 2
;
palmitic acid
;
proopiomelanocortin
;
protein kinase b
;
sc365062
;
stearic acid
;
voltage dependent anion channel
;
insulin
;
proopiomelanocortin
;
stearic acid derivative
;
animal cell
;
article
;
chaperone-mediated autophagy
;
controlled study
;
fluorescence microscopy
;
gene expression
;
genetic transfection
;
hypothalamic cell line
;
immunofluorescence assay
;
in vitro study
;
insulin resistance
;
insulin response
;
insulin treatment
;
lysosome
;
mass spectrometry
;
nonhuman
;
obesity
;
protein expression
;
proteomics
;
real time reverse transcription polymerase chain reaction
;
western blotting
;
human
;
metabolism
;
nerve cell
;
obesity