Endocrine Abstracts

Cardiovascular diseases are the greatest cause of death globally. Obesity significantly increases the risk for the development of cardiovascular diseases. However research does not under stand the physiological and molecular connections of these diseases. We have identified that the hormone leptin in obesity plays a key role in elevating blood pressure in obesity. However recent findings in humans treated with leptin in the disease state of lipodystrophy, did not result in the elevation of blood pressure. In the research present here we suggest that one reason as to why leptin fails to increase blood pressure in lipodystrophy patients is that plasma leptin concentration in not increasing high enough. For the development of cardiovascular complications in obesity plasma leptin concentration needs to increase significantly to concentrations similar to that of obese animals (ten times the concentration measured in lean animals). In rodents we dose dependently demonstrate the differing effects of concentrations of leptin on changes in body weight, food intake, brown adipose tissue temperature, blood pressure and heart rate. We can demonstrated in obese hypertensive mice that changes to the signaling components of specific neurons within the Dorsomedial Hypothalamic leptin receptor expressing neurons in the brain can substantially change leptin’s influence on cardiovascular control. Hence we can control in rodents the development of hypertension in obesity, via manipulating the responsiveness of leptin receptor responsive neurons. We are mapping the connections of this specific subset of neurons and are gaining a true understanding on how the adipose derived hormone leptin plays a key role in the development of cardiovascular diseases.