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

Autor: Sergio Lavandero, Gabriela Yuri, Mariana Cifuentes, Sofía Sanhueza, Assaf Rudich, Claudio E. Perez-Leighton, Pamela Mattar, Lautaro Briones
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Adult
Male
medicine.medical_specialty
autophagy
obesity
calcium-sensing receptor
MAP Kinase Signaling System
ATG5
Adipose tissue
Intra-Abdominal Fat
Autophagy-Related Protein 7
Catalysis
Article
Proinflammatory cytokine
lcsh:Chemistry
Inorganic Chemistry
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Internal medicine
medicine
Adipocytes
Humans
Physical and Theoretical Chemistry
visceral adipose tissue
Receptor
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Cells
Cultured
Chemistry
Tumor Necrosis Factor-alpha
Organic Chemistry
Autophagy
General Medicine
Middle Aged
Computer Science Applications
030104 developmental biology
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
030220 oncology & carcinogenesis
Tumor necrosis factor alpha
Beclin-1
Female
Calcium-sensing receptor
Microtubule-Associated Proteins
Receptors
Calcium-Sensing
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 21, Iss 7617, p 7617 (2020)
Volume 21
Issue 20
ISSN: 1422-0067
Popis: 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&ndash
56% body fat). We also investigated their association with donors&rsquo
anthropometric variables. Donors&rsquo
% 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&rsquo
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.
Databáze: OpenAIRE
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