Kinin B1 receptor stimulation modulates leptin homeostasis. Evidence for an insulin-dependent mechanism.

Kinins are potent vasoactive and inflammatory peptides generated by kallikreins in blood and tissues that bind to specific receptors named B1 and B2. On the other hand, leptin is an adipocytokine that displays broad effects on energy balance, inflammation and vascular tone. Here we demonstrate that the intravenous administration of the kinin B1 receptor agonist des-Arg9-bradykinin (DBK) in mice leads to significant increase in serum leptin levels. However, incubation of isolated white adipose tissue with DBK was not sufficient to induce leptin release or leptin mRNA overexpression. On the contrary, long-term DBK treatment in isolated fat tissue impaired insulin-mediated actions on leptin secretion and expression. In order to verify whether the in vivo effect of B1 receptor stimulation on leptin release was also dependent on blood insulin levels, DBK was injected in animals in hyperinsulinemic state. In this case, however, DBK was not able to potentiate leptinemia. Therefore, our results show that the B1 receptor stimulation may modulate leptin homeostasis in an insulin-dependent manner. These new findings contribute to a better understanding of the processes involving leptin regulation and highlight the involvement of kinins with metabolic processes.