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.
Highlights
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
To investigate the role of adipocyte CaSR on atherogenesis, AdipoqCre+ Casrflox Apoe−/− and AdipoqCre− Casrflox Apoe−/− mice were injected with tamoxifen and fed a high-fat diet (HFD) for 4 weeks (Fig. 1a)
Collagen content was not changed upon adipocyte CaSR deficiency (Fig. 1f)
Summary
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. Adipose tissues enlarge and release many different products, like a dipokines3,4, chemokines[5,6], fatty acids, micro-particles and reactive oxygen species that have a wide range of targets One of these targets is the cardiovascular system leading to vascular inflammation, accumulation of lipids and atherosclerosis[7]. As adipose tissue builds-up and inflammation contributes to systemic inflammation[8], it is likely that stimulation of these processes by CaSR plays a role in atherosclerosis development. We generated mature adipocyte specific CaSR deficient mice on an atherosclerosis prone background, to determine whether adipocyte CaSR exacerbates atherosclerosis development by stimulating adipose tissue inflammation in-vivo
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