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Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: Implications for apoptosis and inflammation

Endoplasmic reticulum (ER) stress and inflammation induced by obesity lead to adipocyte dysfunction, with the impairment of the insulin pathway. Recent studies have indicated that understanding the physiological role of autophagy is of great significance. In the present study, an in vitro model was...

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Autores principales: YIN, JIAJING, WANG, YUFAN, GU, LIPING, FAN, NENGGUANG, MA, YUHANG, PENG, YONGDE
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356450/
https://www.ncbi.nlm.nih.gov/pubmed/25647410
http://dx.doi.org/10.3892/ijmm.2015.2085
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author YIN, JIAJING
WANG, YUFAN
GU, LIPING
FAN, NENGGUANG
MA, YUHANG
PENG, YONGDE
author_facet YIN, JIAJING
WANG, YUFAN
GU, LIPING
FAN, NENGGUANG
MA, YUHANG
PENG, YONGDE
author_sort YIN, JIAJING
collection PubMed
description Endoplasmic reticulum (ER) stress and inflammation induced by obesity lead to adipocyte dysfunction, with the impairment of the insulin pathway. Recent studies have indicated that understanding the physiological role of autophagy is of great significance. In the present study, an in vitro model was used in which 3T3-L1 adipocytes were pre-loaded with palmitate (PA) to generate artificially hypertrophied mature adipocytes. PA induced an autophagic flux, determined by an increased microtubule-associated protein 1 light chain 3 (LC3)-II formation, as shown by western blot analysis and fluorescence microscopy, and was confirmed using transmission electron microscopy (TEM). Using TEM and western blot analysis, we observed increased ER stress in response to PA, as indicated by the increased levels of the ER stress markers, BiP, activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and the phosphoralytion of eukaryotic translation initiation factor 2α and c-Jun N-terminal kinase (JNK). Of note, we observed that the PA-induced ER stress occurred prior to the activation of autophagy. We confirmed that autophagy was induced in response to JNK-dependent ER stress, as autophagy was suppressed by treatment with the ER stress inhibitor, 4-phenyl butyrate (4-PBA), and the JNK inhibitor, SP600125. Upon the inhibition of autophagy using chloroquine (CQ), we observed exacerbated ER stress and an increased level of cell death. Importantly, to determine whether autophagy is linked to inflammation, the autophagy inhibitor, 3-methyladenine (3-MA) was used. The inhibition of autophagy led to a further increase in the PA-induced expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). Consistently, such an increase was also observed following treatment with SP600125. In conclusion, our data indicate that PA elicits a ER stress-JNK-autophagy axis, and that this confers a pro-survival effect against PA-induced cell death and stress in hypertrophied adipocytes. The JNK-dependent activation of autophagy diminishes PA-induced inflammation. Therefore, the stimulation of autophagy may become a method with which to attenuate adipocyte dysfunction and inflammation.
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spelling pubmed-43564502015-03-18 Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: Implications for apoptosis and inflammation YIN, JIAJING WANG, YUFAN GU, LIPING FAN, NENGGUANG MA, YUHANG PENG, YONGDE Int J Mol Med Articles Endoplasmic reticulum (ER) stress and inflammation induced by obesity lead to adipocyte dysfunction, with the impairment of the insulin pathway. Recent studies have indicated that understanding the physiological role of autophagy is of great significance. In the present study, an in vitro model was used in which 3T3-L1 adipocytes were pre-loaded with palmitate (PA) to generate artificially hypertrophied mature adipocytes. PA induced an autophagic flux, determined by an increased microtubule-associated protein 1 light chain 3 (LC3)-II formation, as shown by western blot analysis and fluorescence microscopy, and was confirmed using transmission electron microscopy (TEM). Using TEM and western blot analysis, we observed increased ER stress in response to PA, as indicated by the increased levels of the ER stress markers, BiP, activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and the phosphoralytion of eukaryotic translation initiation factor 2α and c-Jun N-terminal kinase (JNK). Of note, we observed that the PA-induced ER stress occurred prior to the activation of autophagy. We confirmed that autophagy was induced in response to JNK-dependent ER stress, as autophagy was suppressed by treatment with the ER stress inhibitor, 4-phenyl butyrate (4-PBA), and the JNK inhibitor, SP600125. Upon the inhibition of autophagy using chloroquine (CQ), we observed exacerbated ER stress and an increased level of cell death. Importantly, to determine whether autophagy is linked to inflammation, the autophagy inhibitor, 3-methyladenine (3-MA) was used. The inhibition of autophagy led to a further increase in the PA-induced expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). Consistently, such an increase was also observed following treatment with SP600125. In conclusion, our data indicate that PA elicits a ER stress-JNK-autophagy axis, and that this confers a pro-survival effect against PA-induced cell death and stress in hypertrophied adipocytes. The JNK-dependent activation of autophagy diminishes PA-induced inflammation. Therefore, the stimulation of autophagy may become a method with which to attenuate adipocyte dysfunction and inflammation. D.A. Spandidos 2015-04 2015-01-30 /pmc/articles/PMC4356450/ /pubmed/25647410 http://dx.doi.org/10.3892/ijmm.2015.2085 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
YIN, JIAJING
WANG, YUFAN
GU, LIPING
FAN, NENGGUANG
MA, YUHANG
PENG, YONGDE
Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: Implications for apoptosis and inflammation
title Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: Implications for apoptosis and inflammation
title_full Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: Implications for apoptosis and inflammation
title_fullStr Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: Implications for apoptosis and inflammation
title_full_unstemmed Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: Implications for apoptosis and inflammation
title_short Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: Implications for apoptosis and inflammation
title_sort palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: implications for apoptosis and inflammation
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356450/
https://www.ncbi.nlm.nih.gov/pubmed/25647410
http://dx.doi.org/10.3892/ijmm.2015.2085
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