Opera Medica et Physiologica

Calcium-Sensing Receptor Activation Enhances Expression of Lipolysis Activator Genes Through Calcium-Dependent ATP Secretion in White Adipocytes


Using the methods of fluorescence microscopy, Tirf microscopy, inhibitory analysis, immunocytochemistry and PCR, it has been shown that in response to an increase in [Ca2+]o or a CaSR agonist – protamine in the minor population of white adipocytes, Ca2+ signals are rapidly generated – a short-term Ca2+ increase and Ca2+-oscillations, while in most cells the generation of Ca2+ responses occurs after a lag period of varying duration. White adipocyte signals for CaSR activation were completely suppressed in the presence of the selective CaSR antagonist, NPS2143, in both cell populations. When CaSR is activated, a calcium-dependent process of secretion of ATP-containing vesicles occurs, which was also suppressed by NPS2143 and a calcium-dependent secretion blocker tetanus toxin. After a 24- hour exposure to the CaSR activator protamine on white adipocytes, an increase in the level of expression of genes – Lipe, Atgl, Sirt1 and Sirt3, encoding hormone-sensitive lipase, triglyceride lipase, sirtuins 1 and 3, respectively. At the same time, an increase in the expression of these genes was not observed with the selective CaSR antagonist, NPS2143. Thus, one of the new mechanisms of activation of genes regulating white adipose tissue lipolysis can be assumed through an increase in [Ca2+]i in the minor population of CaSR-expressing adipocytes, followed by calcium-dependent ATP secretion and paracrine activation of the entire cell network, which will help play an important role in the regulation of the balance of lipogenesis/lipolysis processes.