Angiotensin II activates different calcium signaling pathways in adipocytes

Angiotensin II (Ang II) is an important mammalian neurohormone involved in reninangiotensin system. Ang II is produced both constitutively and locally by RAS systems, including white fat adipocytes. The influence of Ang II on adipocytes is complex, affecting different systems of signal transduction from early Ca2+ responses to cell proliferation and differentiation, triglyceride accumulation, expression of adipokine-encoding genes and adipokine secretion. It is known that white fat adipocytes express all RAS components and Ang II receptors (AT(1) and AT(2)). The current work was carried out with the primary white adipocytes culture, and Ca2+ signaling pathways activated by Ang II were investigated using fluorescent microscopy. Ca2+-oscillations and transient responses of differentiated adipocytes to Ang II were registered in cells with both small and multiple lipid inclusions. Using inhibitory analysis and selective antagonists, we now show that Ang II initiates periodic Ca2+-oscillations and transient responses by activating AT1 and AT2 receptors and involving branched signaling cascades: 1) Ang II -> Gq -> PLC -> IP3 -> IP(3)Rs -> Ca2+ 2) G beta gamma -> PI3K gamma -> PKB 3) PKB -> eNOS -> NO -> PKG 4) CD38 -> cADPR -> RyRs -> Ca2+ In these cascades, AT(1) receptors play the leading role. The results of the present work open a perspective of using Ang II for correction of signal resistance of adipocytes often observed during obesity and type 2diabetes. (C) 2016 Elsevier Inc. All rights reserved.