Dataset Information

Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe^-/- mice.

ABSTRACT: The calcium sensing receptor (CaSR) is a G-protein coupled receptor that especially plays an important role in the sensing of extracellular calcium to maintain its homeostasis. Several in-vitro studies demonstrated that CaSR plays a role in adipose tissue metabolism and inflammation, resulting in systemic inflammation and contributing to atherosclerosis development. The aim of this study was to investigate whether adipocyte CaSR plays a role in adipose tissue inflammation in-vivo and atherosclerosis development. By using a newly established conditional mature adipocyte specific CaSR deficient mouse on a hyperlipidemic and atherosclerosis prone Apoe^-/- background it could be shown that CaSR deficiency in adipocytes does neither contribute to initiation nor to progression of atherosclerotic plaques as judged by the unchanged lesion size or composition. Additionally, CaSR deficiency did not influence gonadal visceral adipose tissue (vAT) inflammation in-vivo, although a small decrease in gonadal visceral adipose cholesterol content could be observed. In conclusion, adipocyte CaSR seems not to be involved in vAT inflammation in-vivo and does not influence atherosclerosis development in hyperlipidemic Apoe^-/- mice.

SUBMITTER: Sundararaman SS

PROVIDER: S-EPMC8128899 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe<sup>-/-</sup> mice.

Sundararaman Sai Sahana SS Peters Linsey J F LJF Jansen Yvonne Y Gencer Selin S Yan Yi Y Nazir Sumra S Bonnin Marquez Andrea A Kahles Florian F Lehrke Michael M Biessen Erik A L EAL Jankowski Joachim J Weber Christian C Döring Yvonne Y van der Vorst Emiel P C EPC

Scientific reports 20210517 1

The calcium sensing receptor (CaSR) is a G-protein coupled receptor that especially plays an important role in the sensing of extracellular calcium to maintain its homeostasis. Several in-vitro studies demonstrated that CaSR plays a role in adipose tissue metabolism and inflammation, resulting in systemic inflammation and contributing to atherosclerosis development. The aim of this study was to investigate whether adipocyte CaSR plays a role in adipose tissue inflammation in-vivo and atheroscler ...[more]

PMID: 34001955

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Project description:BackgroundChronic unpredictable mild stress (CUMS) has been shown to exacerbate atherosclerosis, but the underlying mechanism remains unknown. Adipose tissue is an energy storage organ and the largest endocrine organ in the human body, playing a key role in the development of cardiovascular disease. In this research, it was hypothesized that CUMS may exacerbate the development of atherosclerosis by inducing the hypertrophy and dysfunction of white adipocytes.MethodsThe CUMS-induced atherosclerosis model was developed in Western diet-fed apolipoprotein E (ApoE)-/- mice. White adipose tissue (WAT), serum, aortic root, and the brachiocephalic trunk were collected and tested after 12 weeks of CUMS development. The mouse model of CUMS was evaluated for depression-like behavior using the open field test (OFT) and the elevated plus maze (EPM) test. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect serum noradrenaline and urine adrenaline protein levels. Serological assays were used to detect serum low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), and free fatty acid (FFA) concentrations. Hematoxylin and eosin (H&E) staining and oil red O were used to detect atherosclerotic plaque area, lipid deposition, and adipocyte size. The mRNA levels of genes related to aberrant adipose tissue function were determined using real-time PCR. Immunofluorescence assay and western blotting were conducted to examine the expression of proteins in the adipose tissue samples.ResultsCUMS aggravated vascular atherosclerotic lesions in ApoE-/- mice. It decreased body weight while increasing the percentage of WAT. The serological results indicated that the concentration of HDL decreased in CUMS mice. Notably, adipocyte hypertrophy increased, whereas the mRNA levels of Pparg and its target genes (Slc2a4 (encodes for GLUT4), Adipoq, and Plin1) decreased. Further investigation revealed that CUMS increased subcutaneous inguinal WAT (iWAT) lipid synthesis and adipocyte inflammation while decreasing lipid hydrolysis and the expression of HDL-associated protein ApoA-I. Moreover, CUMS aggravated insulin resistance in mice and inhibited the insulin pathway in iWAT.ConclusionsThese findings indicated that CUMS induces adipose tissue dysfunction via a mechanism that leads to dyslipidemia, increased inflammation, and insulin resistance in the body, thereby exacerbating atherosclerosis. Notably, CUMS that is involved in decreasing the expression of HDL-associated proteins in adipose tissue may be a crucial link between adipose hypertrophy and advanced atherosclerosis. This study reveals a novel mechanism via which CUMS exacerbates atherosclerosis from the novel perspective of abnormal adipose function and identifies a novel potential therapeutic target for this disease.

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Dataset Information

Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe^-/- mice.

Publications

Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe<sup>-/-</sup> mice.

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Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe-/- mice.

Publications

Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe<sup>-/-</sup> mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Adipocyte calcium sensing receptor is not involved in visceral adipose tissue inflammation or atherosclerosis development in hyperlipidemic Apoe^-/- mice.