Leptin is essential in maintaining normal vascular compliance independent of body weight

The adipocytokine leptin centrally regulates body weight by enhancing metabolic rate and signaling satiety, but it also has wide-ranging peripheral effects. Leptin receptors are expressed on vascular smooth muscle cells and have a role in maintaining vascular tone. We investigated the vascular effects of leptin repletion or calorie restriction on leptin-deficient mice (ob/ob) and a leptin antagonist on wild-type (WT) mice. Aortic compliance was assessed by the measurement of pulse wave velocity by noninvasive Doppler; blood pressure was measured by left ventricular catheterization. We found that ob/ob mice have much stiffer aortas than WT mice and that reduction in aortic stiffness was greater in ob/ob mice treated with leptin vs calorie restriction, despite similar weight loss. Interestingly, treating WT mice with a leptin antagonist increases aortic stiffness with no change in weight. Thus, we conclude that leptin is essential for maintaining normal aortic compliance independent of body weight.