Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy
Open Access
- 15 October 2020
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 21 (20), 7617
- https://doi.org/10.3390/ijms21207617
Abstract
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.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (SFB 1052/1: “Obesity mechanisms” grant (project B2))
This publication has 51 references indexed in Scilit:
- Macrophage-Induced Adipose Tissue Dysfunction and the Preadipocyte: Should I Stay (and Differentiate) or Should I Go?Advances in Nutrition: An International Review Journal, 2013
- Biased agonism of the calcium-sensing receptorCell Calcium, 2012
- Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptorsNature Communications, 2012
- The Calcium-Sensing Receptor Affects Fat Accumulation via Effects on Antilipolytic Pathways in Adipose Tissue of Rats Fed Low-Calcium DietsJournal of Nutrition, 2011
- Obesity-associated proinflammatory cytokines increase calcium sensing receptor (CaSR) protein expression in primary human adipocytes and LS14 human adipose cell lineArchives of Biochemistry and Biophysics, 2010
- Defective Hepatic Autophagy in Obesity Promotes ER Stress and Causes Insulin ResistanceCell Metabolism, 2010
- Adipose-specific deletion of autophagy-related gene 7 ( atg7 ) in mice reveals a role in adipogenesisProceedings of the National Academy of Sciences of the United States of America, 2009
- Autophagy regulates adipose mass and differentiation in miceJCI Insight, 2009
- Calcium-sensing Receptor Gene Transcription Is Up-regulated by the Proinflammatory Cytokine, Interleukin-1βOnline Journal of Public Health Informatics, 2005
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001