Garella Rachele, Bernacchioni Caterina, Chellini Flaminia, Tani Alessia, Palmieri Francesco, Parigi Martina, Guasti Daniele, Cassioli Emanuele, Castellini Giovanni, Ricca Valdo, Bani Daniele, Sassoli Chiara, Donati Chiara, Squecco Roberta
Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, 50134 Florence, Italy.
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50134 Florence, Italy.
Life (Basel). 2023 Aug 26;13(9):1812. doi: 10.3390/life13091812.
Adipokines are peptide hormones produced by the adipose tissue involved in several biological functions. Among adipokines, adiponectin (ADPN) has antidiabetic and anti-inflammatory properties. It can also modulate food intake at central and peripheral levels, acting on hypothalamus and facilitating gastric relaxation. ADPN exerts its action interacting with two distinct membrane receptors and triggering some well-defined signaling cascades. The ceramidase activity of ADPN receptor has been reported in many tissues: it converts ceramide into sphingosine. In turn, sphingosine kinase (SK) phosphorylates it into sphingosine-1 phosphate (S1P), a crucial mediator of many cellular processes including contractility. Using a multidisciplinary approach that combined biochemical, electrophysiological and morphological investigations, we explored for the first time the possible role of S1P metabolism in mediating ADPN effects on the murine gastric fundus muscle layer. By using a specific pharmacological inhibitor of SK2, we showed that ADPN affects smooth muscle cell membrane properties and contractile machinery via SK2 activation in gastric fundus, adding a piece of knowledge to the action mechanisms of this hormone. These findings help to identify ADPN and its receptors as new therapeutic targets or as possible prognostic markers for diseases with altered energy balance and for pathologies with fat mass content alterations.
脂肪因子是由脂肪组织产生的参与多种生物学功能的肽类激素。在脂肪因子中，脂联素（ADPN）具有抗糖尿病和抗炎特性。它还能在中枢和外周水平调节食物摄入，作用于下丘脑并促进胃舒张。ADPN通过与两种不同的膜受体相互作用并触发一些明确的信号级联反应来发挥其作用。ADPN受体的神经酰胺酶活性已在许多组织中被报道：它将神经酰胺转化为鞘氨醇。反过来，鞘氨醇激酶（SK）将其磷酸化为1-磷酸鞘氨醇（S1P），S1P是包括收缩性在内的许多细胞过程的关键介质。我们首次采用结合生化、电生理和形态学研究的多学科方法，探讨了S1P代谢在介导ADPN对小鼠胃底肌层作用中的可能作用。通过使用SK2的特异性药理抑制剂，我们表明ADPN通过激活胃底中的SK2影响平滑肌细胞膜特性和收缩机制，为这种激素的作用机制增添了一项知识。这些发现有助于将ADPN及其受体确定为能量平衡改变的疾病以及脂肪量含量改变的病理状况的新治疗靶点或可能的预后标志物。
