Calcium-sensing receptor in adipose tissue: Possible association with obesity-related elevated autophagy

Pamela Mattar; Sofía Sanhueza; Gabriela Yuri; Lautaro Briones; Claudio Perez-Leighton; Assaf Rudich; Sergio Lavandero; Mariana Cifuentes

doi:10.3390/ijms21207617

Calcium-sensing receptor in adipose tissue: Possible association with obesity-related elevated autophagy

Pamela Mattar, Sofía Sanhueza, Gabriela Yuri, Lautaro Briones, Claudio Perez-Leighton, Assaf Rudich, Sergio Lavandero, Mariana Cifuentes

Universidad de Chile

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

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.

Original language	English
Article number	7617
Pages (from-to)	1-14
Number of pages	14
Journal	International Journal of Molecular Sciences
Volume	21
Issue number	20
DOIs	https://doi.org/10.3390/ijms21207617
Publication status	Published - Oct 2 2020

Bibliographical note

Publisher Copyright:
© 2020 by the authors.

Funding

Funding: This work was supported by grants from the Agencia Nacional de Investigación y Desarrollo (ANID), Chile: FONDECYT 1150651 to MC and 1200490 to SL, FONDAP 15130011 to SL and MC and FONDECYT 1152075 to CPL. PhD Fellowship CONICYT 21130162 and post-doctoral Fellowship FONDECYT 3190416 to PM. Deutsche Forschungsgemeinschaft (DFG): SFB 1052/1: “Obesity mechanisms” grant (project B2) support to AR.

Funders	Funder number
Fogarty International Center	D43TW011506
Deutsche Forschungsgemeinschaft	SFB 1052/1
Comisión Nacional de Investigación Científica y Tecnológica	21130162, 3190416
Fondo Nacional de Desarrollo Científico y Tecnológico	1152075, 15130011, 1200490, 1150651
Agencia de Innovación y Desarrollo de Andalucía

ASJC Scopus Subject Areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/ijms21207617

Cite this

@article{f5960a362cb9412b8bba7f84dc96ce56,

title = "Calcium-sensing receptor in adipose tissue: Possible association with obesity-related elevated autophagy",

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{\textquoteright} anthropometric variables. Donors{\textquoteright} % 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{\textquoteright} 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.",

author = "Pamela Mattar and Sof{\'i}a Sanhueza and Gabriela Yuri and Lautaro Briones and Claudio Perez-Leighton and Assaf Rudich and Sergio Lavandero and Mariana Cifuentes",

note = "Publisher Copyright: {\textcopyright} 2020 by the authors.",

year = "2020",

month = oct,

day = "2",

doi = "10.3390/ijms21207617",

language = "English",

volume = "21",

pages = "1--14",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "20",

}

TY - JOUR

T1 - Calcium-sensing receptor in adipose tissue

T2 - Possible association with obesity-related elevated autophagy

AU - Mattar, Pamela

AU - Sanhueza, Sofía

AU - Yuri, Gabriela

AU - Briones, Lautaro

AU - Perez-Leighton, Claudio

AU - Rudich, Assaf

AU - Lavandero, Sergio

AU - Cifuentes, Mariana

PY - 2020/10/2

Y1 - 2020/10/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85092890342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85092890342&partnerID=8YFLogxK

U2 - 10.3390/ijms21207617

DO - 10.3390/ijms21207617

M3 - Article

C2 - 33076271

AN - SCOPUS:85092890342

SN - 1661-6596

VL - 21

SP - 1

EP - 14

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 20

M1 - 7617

ER -

Calcium-sensing receptor in adipose tissue: Possible association with obesity-related elevated autophagy

Abstract

Bibliographical note

Funding

ASJC Scopus Subject Areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this