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Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy

Autophagy is upregulated in adipose tissue (AT) from people with obesity. We showed that activation of the calcium-sensing receptor (CaSR) elevates proinflammatory cytokines through autophagy in preadipocytes. Our aim is to understand the role of CaSR on autophagy in AT from humans with obesity. We...

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Autores principales: Mattar, Pamela, Sanhueza, Sofía, Yuri, Gabriela, Briones, Lautaro, Perez-Leighton, Claudio, Rudich, Assaf, Lavandero, Sergio, Cifuentes, Mariana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590196/
https://www.ncbi.nlm.nih.gov/pubmed/33076271
http://dx.doi.org/10.3390/ijms21207617
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author Mattar, Pamela
Sanhueza, Sofía
Yuri, Gabriela
Briones, Lautaro
Perez-Leighton, Claudio
Rudich, Assaf
Lavandero, Sergio
Cifuentes, Mariana
author_facet Mattar, Pamela
Sanhueza, Sofía
Yuri, Gabriela
Briones, Lautaro
Perez-Leighton, Claudio
Rudich, Assaf
Lavandero, Sergio
Cifuentes, Mariana
author_sort Mattar, Pamela
collection PubMed
description Autophagy is upregulated in adipose tissue (AT) from people with obesity. We showed that activation of the calcium-sensing receptor (CaSR) elevates proinflammatory cytokines through autophagy in preadipocytes. Our aim is to understand the role of CaSR on autophagy in AT from humans with obesity. We determined mRNA and protein levels of CaSR and markers of autophagy by qPCR and western blot in human visceral AT explants or isolated primary preadipocytes (60 donors: 72% female, 23–56% body fat). We also investigated their association with donors’ anthropometric variables. Donors’ % body fat and CaSR mRNA expression in AT were correlated (r = 0.44, p < 0.01). CaSR expression was associated with mRNA levels of the autophagy markers atg5 (r = 0.37, p < 0.01), atg7 (r = 0.29, p < 0.05) and lc3b (r = 0.40, p < 0.01). CaSR activation increased becn and atg7 mRNA expression in AT. CaSR activation also upregulated LC3II by ~50%, an effect abolished by the CaSR inhibitor. Spermine (CaSR agonist) regulates LC3II through the ERK1/2 pathway. Structural equation model analysis suggests a link between donors’ AT CaSR expression, AT autophagy and expression of Tumor Necrosis Factor alpha TNF-α. CaSR expression in visceral AT is directly associated with % body fat, and CaSR activation may contribute to obesity-related disruption in AT autophagy.
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spelling pubmed-75901962020-10-29 Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy Mattar, Pamela Sanhueza, Sofía Yuri, Gabriela Briones, Lautaro Perez-Leighton, Claudio Rudich, Assaf Lavandero, Sergio Cifuentes, Mariana Int J Mol Sci Article Autophagy is upregulated in adipose tissue (AT) from people with obesity. We showed that activation of the calcium-sensing receptor (CaSR) elevates proinflammatory cytokines through autophagy in preadipocytes. Our aim is to understand the role of CaSR on autophagy in AT from humans with obesity. We determined mRNA and protein levels of CaSR and markers of autophagy by qPCR and western blot in human visceral AT explants or isolated primary preadipocytes (60 donors: 72% female, 23–56% body fat). We also investigated their association with donors’ anthropometric variables. Donors’ % body fat and CaSR mRNA expression in AT were correlated (r = 0.44, p < 0.01). CaSR expression was associated with mRNA levels of the autophagy markers atg5 (r = 0.37, p < 0.01), atg7 (r = 0.29, p < 0.05) and lc3b (r = 0.40, p < 0.01). CaSR activation increased becn and atg7 mRNA expression in AT. CaSR activation also upregulated LC3II by ~50%, an effect abolished by the CaSR inhibitor. Spermine (CaSR agonist) regulates LC3II through the ERK1/2 pathway. Structural equation model analysis suggests a link between donors’ AT CaSR expression, AT autophagy and expression of Tumor Necrosis Factor alpha TNF-α. CaSR expression in visceral AT is directly associated with % body fat, and CaSR activation may contribute to obesity-related disruption in AT autophagy. MDPI 2020-10-15 /pmc/articles/PMC7590196/ /pubmed/33076271 http://dx.doi.org/10.3390/ijms21207617 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mattar, Pamela
Sanhueza, Sofía
Yuri, Gabriela
Briones, Lautaro
Perez-Leighton, Claudio
Rudich, Assaf
Lavandero, Sergio
Cifuentes, Mariana
Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy
title Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy
title_full Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy
title_fullStr Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy
title_full_unstemmed Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy
title_short Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy
title_sort calcium-sensing receptor in adipose tissue: possible association with obesity-related elevated autophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590196/
https://www.ncbi.nlm.nih.gov/pubmed/33076271
http://dx.doi.org/10.3390/ijms21207617
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