Urocortin 3 overexpression reduces ER stress and heat shock response in 3T3-L1 adipocytes

Abstract The neuropeptide urocortin 3 (UCN3) has a beneficial effect on metabolic disorders, such as obesity, diabetes, and cardiovascular disease. It has been reported that UCN3 regulates insulin secretion and is dysregulated with increasing severity of obesity and diabetes. However, its function i...

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Autores principales:	Sina Kavalakatt, Abdelkrim Khadir, Dhanya Madhu, Heikki A. Koistinen, Fahd Al-Mulla, Jaakko Tuomilehto, Jehad Abubaker, Ali Tiss
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f231d71be668489eae2c831192bc9068
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spelling	oai:doaj.org-article:f231d71be668489eae2c831192bc90682021-12-02T17:06:09ZUrocortin 3 overexpression reduces ER stress and heat shock response in 3T3-L1 adipocytes10.1038/s41598-021-95175-42045-2322https://doaj.org/article/f231d71be668489eae2c831192bc90682021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95175-4https://doaj.org/toc/2045-2322Abstract The neuropeptide urocortin 3 (UCN3) has a beneficial effect on metabolic disorders, such as obesity, diabetes, and cardiovascular disease. It has been reported that UCN3 regulates insulin secretion and is dysregulated with increasing severity of obesity and diabetes. However, its function in the adipose tissue is unclear. We investigated the overexpression of UCN3 in 3T3-L1 preadipocytes and differentiated adipocytes and its effects on heat shock response, ER stress, inflammatory markers, and glucose uptake in the presence of stress-inducing concentrations of palmitic acid (PA). UCN3 overexpression significantly downregulated heat shock proteins (HSP60, HSP72 and HSP90) and ER stress response markers (GRP78, PERK, ATF6, and IRE1α) and attenuated inflammation (TNFα) and apoptosis (CHOP). Moreover, enhanced glucose uptake was observed in both preadipocytes and mature adipocytes, which is associated with upregulated phosphorylation of AKT and ERK but reduced p-JNK. Moderate effects of UCN3 overexpression were also observed in the presence of 400 μM of PA, and macrophage conditioned medium dramatically decreased the UCN3 mRNA levels in differentiated 3T3-L1 cells. In conclusion, the beneficial effects of UCN3 in adipocytes are reflected, at least partially, by the improvement in cellular stress response and glucose uptake and attenuation of inflammation and apoptosis.Sina KavalakattAbdelkrim KhadirDhanya MadhuHeikki A. KoistinenFahd Al-MullaJaakko TuomilehtoJehad AbubakerAli TissNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sina Kavalakatt Abdelkrim Khadir Dhanya Madhu Heikki A. Koistinen Fahd Al-Mulla Jaakko Tuomilehto Jehad Abubaker Ali Tiss Urocortin 3 overexpression reduces ER stress and heat shock response in 3T3-L1 adipocytes
description	Abstract The neuropeptide urocortin 3 (UCN3) has a beneficial effect on metabolic disorders, such as obesity, diabetes, and cardiovascular disease. It has been reported that UCN3 regulates insulin secretion and is dysregulated with increasing severity of obesity and diabetes. However, its function in the adipose tissue is unclear. We investigated the overexpression of UCN3 in 3T3-L1 preadipocytes and differentiated adipocytes and its effects on heat shock response, ER stress, inflammatory markers, and glucose uptake in the presence of stress-inducing concentrations of palmitic acid (PA). UCN3 overexpression significantly downregulated heat shock proteins (HSP60, HSP72 and HSP90) and ER stress response markers (GRP78, PERK, ATF6, and IRE1α) and attenuated inflammation (TNFα) and apoptosis (CHOP). Moreover, enhanced glucose uptake was observed in both preadipocytes and mature adipocytes, which is associated with upregulated phosphorylation of AKT and ERK but reduced p-JNK. Moderate effects of UCN3 overexpression were also observed in the presence of 400 μM of PA, and macrophage conditioned medium dramatically decreased the UCN3 mRNA levels in differentiated 3T3-L1 cells. In conclusion, the beneficial effects of UCN3 in adipocytes are reflected, at least partially, by the improvement in cellular stress response and glucose uptake and attenuation of inflammation and apoptosis.
format	article
author	Sina Kavalakatt Abdelkrim Khadir Dhanya Madhu Heikki A. Koistinen Fahd Al-Mulla Jaakko Tuomilehto Jehad Abubaker Ali Tiss
author_facet	Sina Kavalakatt Abdelkrim Khadir Dhanya Madhu Heikki A. Koistinen Fahd Al-Mulla Jaakko Tuomilehto Jehad Abubaker Ali Tiss
author_sort	Sina Kavalakatt
title	Urocortin 3 overexpression reduces ER stress and heat shock response in 3T3-L1 adipocytes
title_short	Urocortin 3 overexpression reduces ER stress and heat shock response in 3T3-L1 adipocytes
title_full	Urocortin 3 overexpression reduces ER stress and heat shock response in 3T3-L1 adipocytes
title_fullStr	Urocortin 3 overexpression reduces ER stress and heat shock response in 3T3-L1 adipocytes
title_full_unstemmed	Urocortin 3 overexpression reduces ER stress and heat shock response in 3T3-L1 adipocytes
title_sort	urocortin 3 overexpression reduces er stress and heat shock response in 3t3-l1 adipocytes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f231d71be668489eae2c831192bc9068
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Urocortin 3 overexpression reduces ER stress and heat shock response in 3T3-L1 adipocytes

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