Leptin Infusion and Endothelial Vasomotor Response

Adipose tissue is an active endocrine organ producing several hormones with circulatory and metabolic effects. In 1994, the hormone leptin was discovered. The lack of this hormone explained extreme obesity in rare patients and parenteral substitution restored body weight and metabolic disturbances. It was however soon discovered that most humans had too high levels which were related to development of cardiovascular diseases and diabetes. It was hypothesised that leptin induced vessel dysfunction which could explain this association. In this study, we wanted to examine the association between leptin and vessel function by using the venous occlusion plethysmography method. We used three protocols to evaluate this association. First protocol. In ten healthy males, leptin was infused locally in the forearm and forearm blood flow (FBF) was measured. Second protocol. In ten healthy males, leptin or normal saline was infused locally in the forearm and FBF was measured. Concomitantly, four vasodilatators were infused locally in the forearm in a randomised order and the response (blood flow and fibrinolysis) was measured. Third protocol. In eighty-three patients with known coronary artery disease, three vasodilators were infused locally in the forearm in a random order and response (FBF and fibrinolysis) was measured. The response was related to endogenous leptin levels. The two first protocols were performed in Umeå, Sweden whereas the third was performed in Edinburgh, UK, all in 2006.