Ca2+ responses induced by adrenergic agonists in preadipocytes of mouse and ground squirrel (Spermophillus undulates)

Abstract

Brown adipose tissue of small animals in the cold is able to increase several fold its mass and ability for non-shivering thermogenesis. Adrenergic agonists play a crucial role in the stimulation of the tissue hyperplasia and thermoregulation. In this work, a comparative study of the Ca2+ signaling in mouse and ground squirrel brown preadipocytes was carried out. The goal of this study was to elucidate what features of the Ca2+ signaling in ground squirrel preadipocytes allow the hibernators to control brown fat hyperplasia in the absence of cold stress. This knowledge would enable us to find ways to control human body mass and to treat diabetes mellitus type two. Low concentrations (0.3–3 μM for mouse cells and 1–10 μM for ground squirrel cells) of the selective α1- and β-adrenergic agonists cirazoline and isoproterenol, respectively, induced slow Ca2+ responses with linear kinetics in brown preadipocytes of both species. High concentrations of the agonists (10–500 μM) caused Ca2+ responses with exponential kinetics in ground squirrel brown preadipocytes and suppressed the responses in mouse preadipocytes. Dose-response curves for the agonists were bell-shaped for both mouse and ground squirrel preadipocytes. It should be noted that in preadipocytes of both species β-adrenergic agonist induced stronger responses than α1-adrenergic agonist did. On the other hand, the responses evoked in ground squirrel brown preadipocytes by both agonists were two orders of magnitude stronger than the responses in mouse preadipocytes. Treatment of the cells with forskolin demonstrated that brown preadipocytes of a ground squirrel had a strong positive feedback in Ca2+ signaling, whereas mouse preadipocytes had a negative feedback. The difference found in the preadipocyte Ca2+ signaling may explain the different strategies employed in the two species for the regulation of their body fat mass and survival in the cold.