Leptin is an adipocyte-derived hormone that acts directly in the brain reducing food intake, increasing glucose uptake and modulating the metabolism in adipose tissue. Nevertheless, the central mechanisms related to improve glucose uptake, induced by leptin intracerebroventricular (icv), and the proteins activated in the skeletal muscle are incompletely understood. The aim of this study was to investigate the mechanism by which ICV leptin increase glucose uptake and improve glucose homeostasis. Rats were divided into three experimental groups: i) Control (Saline-ICV); Leptin (Leptin-ICV) and LY (Ly294002+ Leptin-ICV). In all these groups were analyzed glucose tolerance (GTT), AKT, JAK2 activation, stimulated by insulin, in the muscle and hypothalamic AKT, JAK2 and STAT3 activation stimulated by leptin. ICV leptin increased the phosphorylation of hypothalamic JAK2 (80%), STAT3 (160%) and AKT (300%) when compared to control group. Previous ICV LY administration reduced AKT phosphorylation, induced by ICV leptin, but didnt present effect on JAK2 and STAT3 phosphorylation. Besides, ICV leptin improve the clearance of glucose in GTT (50%). Previous administration of propranolol (10 mg/kg bw-IP), but not ICV Ly294002 (1 nmol-ICV), reduced the effect of leptin on GTT. In the soleus muscle the AKT phosphorylation, stimulated by insulin, was higher in leptin group (400%) than control group. The previous administration of propranolol (ip) reduced (40%) the effect of ICV leptin on AKT phosphorylation, stimulated by insulin, in skeletal muscle. ICV Ly294002 didnt present effect on AKT phosphorylation, in skeletal muscle. JAK2 phosphorylation was higher in leptin (ICV) group than control group (ICV saline). Our results suggesting that adrenergic signal are activated by central leptin stimulating AKT activation in the skeletal muscle. In the skeletal muscle JAK2 activation is likely a responsible mechanism by AKT activation.
25 - 29 Apr 2009
European Society of Endocrinology