Calcium-Sensing Receptor in Adipose Tissue: Possible Association with Obesity-Related Elevated Autophagy
Author
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Mattar, Pamela
Author
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Pino Sanhueza, Sofía Carolina
Author
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Yuri, Gabriela
Author
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Briones, Lautaro
Author
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Pérez Leighton, Claudio
Author
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Rudich, Assaf
Author
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Lavandero González, Sergio
Author
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Cifuentes Koster, Mariana
Admission date
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2021-05-06T21:47:02Z
Available date
dc.date.available
2021-05-06T21:47:02Z
Publication date
dc.date.issued
2020
Cita de ítem
dc.identifier.citation
Int. J. Mol. Sci. 2020, 21, 7617
es_ES
Identifier
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10.3390/ijms21207617
Identifier
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https://repositorio.uchile.cl/handle/2250/179476
Abstract
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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 similar to 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-alpha. 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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Patrocinador
dc.description.sponsorship
Agencia Nacional de Investigacion y Desarrollo (ANID), Chile
FONDECYT 1150651
1200490
FONDAP 15130011
FONDECYT 1152075
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
21130162
Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT)
CONICYT FONDECYT
3190416
German Research Foundation (DFG)
SFB 1052/1