{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:30:30Z","timestamp":1792042230248,"version":"4.4.0"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa de Investigaci\u00f3n Asociativa PIA-CONICYT","award":["N\u00ba172066"],"award-info":[{"award-number":["N\u00ba172066"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"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>","DOI":"10.3390\/cells11060920","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T12:35:37Z","timestamp":1646742937000},"page":"920","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Palmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro"],"prefix":"10.3390","volume":"11","author":[{"given":"Rodrigo","family":"Espinosa","sequence":"first","affiliation":[{"name":"Molecular and Cellular Pathology Laboratory, Institute in Dentistry Sciences, Dentistry Faculty, University of Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Pathology Laboratory, Institute in Dentistry Sciences, Dentistry Faculty, University of Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javiera","family":"Rios","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Pathology Laboratory, Institute in Dentistry Sciences, Dentistry Faculty, University of Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Orme\u00f1o","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Pathology Laboratory, Institute in Dentistry Sciences, Dentistry Faculty, University of Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Yant\u00e9n","sequence":"additional","affiliation":[{"name":"Centro Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Avda. Za\u00f1artu 1482, \u00d1u\u00f1oa, Santiago 7780272, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Galaz-Davison","sequence":"additional","affiliation":[{"name":"Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 7820436, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4647-903X","authenticated-orcid":false,"given":"C\u00e9sar A.","family":"Ram\u00edrez-Sarmiento","sequence":"additional","affiliation":[{"name":"Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Cat\u00f3lica de Chile, Santiago 7820436, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0080-6472","authenticated-orcid":false,"given":"Valentina","family":"Parra","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas & Facultad de Medicina, Universidad de Chile, Santiago 8380544, Chile"},{"name":"Autophagy Research Center (ARC), Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1030-8650","authenticated-orcid":false,"given":"Amelina","family":"Albornoz","sequence":"additional","affiliation":[{"name":"Centro Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Avda. Za\u00f1artu 1482, \u00d1u\u00f1oa, Santiago 7780272, Chile"},{"name":"Departamento de Ciencias B\u00e1sicas, Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Lota 2465, Santiago 7510157, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5938-5940","authenticated-orcid":false,"given":"Iv\u00e1n E.","family":"Alfaro","sequence":"additional","affiliation":[{"name":"Centro Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Avda. Za\u00f1artu 1482, \u00d1u\u00f1oa, Santiago 7780272, Chile"},{"name":"Programa de Comunicaci\u00f3n Celular en C\u00e1ncer, Instituto de Ciencias e Innovaci\u00f3n en Medicina, Facultad de Medicina, Cl\u00ednica Alemana Universidad del Desarrollo, Santiago 7610658, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia V.","family":"Burgos","sequence":"additional","affiliation":[{"name":"Centro Ciencia & Vida, Fundaci\u00f3n Ciencia & Vida, Avda. Za\u00f1artu 1482, \u00d1u\u00f1oa, Santiago 7780272, Chile"},{"name":"Autophagy Research Center (ARC), Santiago 8380544, Chile"},{"name":"Centro de Biolog\u00eda Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Lota 2465, Santiago 7510157, Chile"},{"name":"Centro de Envejecimiento y Regeneraci\u00f3n (CARE-UC), Facultad de Ciencias Biol\u00f3gicas, Pontificia Universidad Cat\u00f3lica, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Morselli","sequence":"additional","affiliation":[{"name":"Autophagy Research Center (ARC), Santiago 8380544, Chile"},{"name":"Departamento de Ciencias B\u00e1sicas, Facultad de Medicina y Ciencia, Universidad San Sebasti\u00e1n, Lota 2465, Santiago 7510157, Chile"},{"name":"Laboratory of Autophagy and Metabolism, Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Cat\u00f3lica De Chile, Santiago 8331150, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Criollo","sequence":"additional","affiliation":[{"name":"Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas & Facultad de Medicina, Universidad de Chile, Santiago 8380544, Chile"},{"name":"Autophagy Research Center (ARC), Santiago 8380544, Chile"},{"name":"Cellular and Molecular Biology Laboratory, Institute in Dentistry Sciences, Dentistry Faculty, University of Chile, Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1821-291X","authenticated-orcid":false,"given":"Mauricio","family":"Budini","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Pathology Laboratory, Institute in Dentistry Sciences, Dentistry Faculty, University of Chile, Santiago 8380544, Chile"},{"name":"Autophagy Research Center (ARC), Santiago 8380544, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1056\/NEJM196304042681404","article-title":"Plasma Free Fatty Acid Concentrations in Obesity","volume":"268","author":"Opie","year":"1963","journal-title":"N. 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