Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Espinosa, Rodrigo, Gutiérrez, Karla, Rios, Javiera, Ormeño, Fernando, Yantén, Liliana, Galaz-Davison, Pablo, Ramírez-Sarmiento, César A., Parra, Valentina, Albornoz, Amelina, Alfaro, Iván E., Burgos, Patricia V., Morselli, Eugenia, Criollo, Alfredo, Budini, Mauricio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945987/
https://www.ncbi.nlm.nih.gov/pubmed/35326371
http://dx.doi.org/10.3390/cells11060920
_version_ 1784674085965398016
author Espinosa, Rodrigo
Gutiérrez, Karla
Rios, Javiera
Ormeño, Fernando
Yantén, Liliana
Galaz-Davison, Pablo
Ramírez-Sarmiento, César A.
Parra, Valentina
Albornoz, Amelina
Alfaro, Iván E.
Burgos, Patricia V.
Morselli, Eugenia
Criollo, Alfredo
Budini, Mauricio
author_facet Espinosa, Rodrigo
Gutiérrez, Karla
Rios, Javiera
Ormeño, Fernando
Yantén, Liliana
Galaz-Davison, Pablo
Ramírez-Sarmiento, César A.
Parra, Valentina
Albornoz, Amelina
Alfaro, Iván E.
Burgos, Patricia V.
Morselli, Eugenia
Criollo, Alfredo
Budini, Mauricio
author_sort Espinosa, Rodrigo
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8945987
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89459872022-03-25 Palmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro Espinosa, Rodrigo Gutiérrez, Karla Rios, Javiera Ormeño, Fernando Yantén, Liliana Galaz-Davison, Pablo Ramírez-Sarmiento, César A. Parra, Valentina Albornoz, Amelina Alfaro, Iván E. Burgos, Patricia V. Morselli, Eugenia Criollo, Alfredo Budini, Mauricio Cells Article 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. MDPI 2022-03-08 /pmc/articles/PMC8945987/ /pubmed/35326371 http://dx.doi.org/10.3390/cells11060920 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Espinosa, Rodrigo
Gutiérrez, Karla
Rios, Javiera
Ormeño, Fernando
Yantén, Liliana
Galaz-Davison, Pablo
Ramírez-Sarmiento, César A.
Parra, Valentina
Albornoz, Amelina
Alfaro, Iván E.
Burgos, Patricia V.
Morselli, Eugenia
Criollo, Alfredo
Budini, Mauricio
Palmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro
title Palmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro
title_full Palmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro
title_fullStr Palmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro
title_full_unstemmed Palmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro
title_short Palmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro
title_sort palmitic and stearic acids inhibit chaperone-mediated autophagy (cma) in pomc-like neurons in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945987/
https://www.ncbi.nlm.nih.gov/pubmed/35326371
http://dx.doi.org/10.3390/cells11060920
work_keys_str_mv AT espinosarodrigo palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT gutierrezkarla palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT riosjaviera palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT ormenofernando palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT yantenliliana palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT galazdavisonpablo palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT ramirezsarmientocesara palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT parravalentina palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT albornozamelina palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT alfaroivane palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT burgospatriciav palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT morsellieugenia palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT criolloalfredo palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro
AT budinimauricio palmiticandstearicacidsinhibitchaperonemediatedautophagycmainpomclikeneuronsinvitro