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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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 |
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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 |
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