Role of β-adrenergic receptors in the anti-obesity and anti-diabetic effects of zinc-α2-glycoprotien (ZAG)

Objectives: The goal of the current study is to determine whether the beta-adrenoreceptor (beta-AR) plays a role in the anti-obesity and anti-diabetic effects of zinc-alpha 2-glycoprotein (ZAG). Material and methods: This has been investigated in CHO-K1 cells transfected with the human beta 1-, beta 2-, beta 3-AR and in ob/ob mice. Cyclic AMP assays were carried out along with binding studies. Ob/ob mice were treated with ZAG and glucose transportation and insulin were examined in the presence or absence of propranolol. Results: ZAG bound to the beta 3-AR with higher affinity (Kd 46 +/- 1 nM) than the beta 2-AR (Kd 71 +/- 3 nM) while there was no binding to the beta 1-AR, and this correlated with the increases in cyclic AMP in CHO-K1 cells transfected with the various beta-AR and treated with ZAG. Treatment of ob/ob mice with ZAG increased protein expression of beta 3-AR in gastrocnemius muscle, and in white and brown adipose tissues, but had no effect on expression of beta 1- and beta 2-AR. A reduction of body weight was seen and urinary glucose excretion, increase in body temperature, reduction in maximal plasma glucose and insulin levels in the oral glucose tolerance test, and stimulation of glucose transport into skeletal muscle and adipose tissue, were completely attenuated by the non-specific beta-AR antagonist propranolol. Conclusion: The results suggest that the effects of ZAG on body weight and insulin sensitivity in ob/ob mice are manifested through a beta-3AR, or possibly a beta 2-AR. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.