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

Cells

Valentina Parra¹  Alfredo Criollo¹  Eugenia Morselli²  Iván E. Alfaro³  Liliana Yantén³  Patricia V. Burgos³  Amelina Albornoz³  Pablo Galaz-Davison⁴  César A. Ramírez-Sarmiento⁴  Javiera Rios⁵  Fernando Ormeño⁵  Mauricio Budini⁵  Karla Gutiérrez⁵  Rodrigo Espinosa⁵ 

[1] Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas & Facultad de Medicina, Universidad de Chile, Santiago 8380544, Chile;Autophagy Research Center (ARC), Santiago 8380544, Chile;Centro Ciencia & Vida, Fundación Ciencia & Vida, Avda. Zañartu 1482, Ñuñoa, Santiago 7780272, Chile;Institute for Biological and Medical Engineering, Schools of Engineering, Medicine and Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile;Molecular and Cellular Pathology Laboratory, Institute in Dentistry Sciences, Dentistry Faculty, University of Chile, Santiago 8380544, Chile;

关键词: chaperone-mediated autophagy (CMA);    insulin;    palmitic;    stearic;    lysosome;    obesity;   

DOI  :  10.3390/cells11060920

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown