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

Mattar, Pamela; Sanhueza, Sofía; Yuri, Gabriela; Briones, Lautaro; Perez‐Leighton, Claudio E.; Rudich, Assaf; Lavandero, Sergio; Cifuentes, Mariana

doi:10.3390/ijms21207617

Cited by 11 publications

(6 citation statements)

References 53 publications

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“…CVDs linked to obesity are mostly due to adipose tissue dysfunction, its enlargement, and the release of inflammatory factors from the adipose tissue [ 82 ]. Enlarged adipose tissues also show higher expression levels of CaSR [ 83 ]. It has been observed that the activation of CaSR in human preadipocytes stimulates autophagy, which is an essential mechanism for cellular homeostasis, because when damaged organelles are not degraded by lysosomes this leads to cardiometabolic comorbidities especially in conditions of obesity [ 84 ].…”

Section: Pathological Role Of Casr In Inflammation and Cardiovascumentioning

confidence: 99%

Calcium-Sensing Receptor (CaSR), Its Impact on Inflammation and the Consequences on Cardiovascular Health

Sundararaman

Vorst

2021

IJMS

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The calcium Sensing Receptor (CaSR) is a cell surface receptor belonging to the family of G-protein coupled receptors. CaSR is mainly expressed by parathyroid glands, kidneys, bone, skin, adipose tissue, the gut, the nervous system, and the cardiovascular system. The receptor, as its name implies is involved in sensing calcium fluctuations in the extracellular matrix of cells, thereby having a major impact on the mineral homeostasis in humans. Besides calcium ions, the receptor is also activated by other di- and tri-valent cations, polypeptides, polyamines, antibiotics, calcilytics and calcimimetics, which upon binding induce intracellular signaling pathways. Recent studies have demonstrated that CaSR influences a wide variety of cells and processes that are involved in inflammation, the cardiovascular system, such as vascular calcification, atherosclerosis, myocardial infarction, hypertension, and obesity. Therefore, in this review, the current understanding of the role that CaSR plays in inflammation and its consequences on the cardiovascular system will be highlighted.

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Section: Pathological Role Of Casr In Inflammation and Cardiovascumentioning

confidence: 99%

Calcium-Sensing Receptor (CaSR), Its Impact on Inflammation and the Consequences on Cardiovascular Health

Sundararaman

Vorst

2021

IJMS

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“…Furthermore, medium conditioned by adipose tissue explants from obese subjects increased CaSR expression in adipocytes and this CaSR expression was positively associated with BMI from the donor 50 . In addition, there is a positive correlation between CaSR mRNA expression in human vAT and fat percentage 51 . Therefore, it is possible that a more extreme condition, like obesity, is needed to distinctively elucidate the role of CaSR on adipose tissue inflammation.…”

Section: Discussionmentioning

confidence: 92%

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

Sundararaman

Peters

Jansen³

et al. 2021

Sci Rep

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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.

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“…CASR exerted complicated functions in prostate, breast and colorectal cancer by regulating calcium homeostasis and inflammation 28–30 . Previous studies have shown that CASR could regulate autophagy in mammalian cells and that activation or overexpression of CASR induced autophagy, whereas inhibition or knockdown of CASR suppressed autophagy, which might be the molecular mechanism by which CASR regulates cancer 31–33 . Therefore, we speculated that NPS‐2143, the selective CASR antagonist, also might exert anti‐glioma ability by suppressing autophagy.…”

Section: Discussionmentioning

confidence: 96%

NPS‐2143 inhibit glioma progression by suppressing autophagy through mediating AKT–mTOR pathway

Nie,

Li,

Yin

et al. 2024

J Cellular Molecular Medi

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Gliomas are the most common tumours in the central nervous system. In the present study, we aimed to find a promising anti‐glioma compound and investigate the underlying molecular mechanism. Glioma cells were subjected to the 50 candidate compounds at a final concentration of 10 μM for 72 h, and CCK‐8 was used to evaluate their cytotoxicity. NPS‐2143, an antagonist of calcium‐sensing receptor (CASR), was selected for further study due to its potent cytotoxicity to glioma cells. Our results showed that NPS‐2143 could inhibit the proliferation of glioma cells and induce G1 phase cell cycle arrest. Meanwhile, NPS‐2143 could induce glioma cell apoptosis by increasing the caspase‐3/6/9 activity. NPS‐2143 impaired the immigration and invasion ability of glioma cells by regulating the epithelial–mesenchymal transition process. Mechanically, NPS‐2143 could inhibit autophagy by mediating the AKT–mTOR pathway. Bioinformatic analysis showed that the prognosis of glioma patients with low expression of CASR mRNA was better than those with high expression of CASR mRNA. Gene set enrichment analysis showed that CASR was associated with cell adhesion molecules and lysosomes in glioma. The nude mice xenograft model showed NPS‐2143 could suppress glioma growth in vivo. In conclusion, NPS‐2143 can suppress the glioma progression by inhibiting autophagy.

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

Cited by 11 publications

References 53 publications

Calcium-Sensing Receptor (CaSR), Its Impact on Inflammation and the Consequences on Cardiovascular Health

Calcium-Sensing Receptor (CaSR), Its Impact on Inflammation and the Consequences on Cardiovascular Health

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

NPS‐2143 inhibit glioma progression by suppressing autophagy through mediating AKT–mTOR pathway

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