The role of fat mass on the development of secondary diseases; specifically the impact of elevated leptin concentration on the development of hypertension

Obesity and the excessive accumulation of body fat is associated with significant chronic secondary diseases including, cardiovascular diseases, cancers and diabetes. Obesity and its associated diseases are becoming huge economic and social problems, due to the number of people being affected and the personal, social and economic costs for their care. Both developed and developing nations are affected. In recent years a number of obesity therapeutics have made it to market and these appear to reduce the body weight associated with obesity, however their effectiveness chronically and in reducing secondary diseases maybe limited. Hence there is a need to mechanically understand the physiology behind the development of both obesity and the secondary diseases developing in obesity so that effective therapies can be created. Cardiovascular diseases are the number 1 cause of death globally and have been since the 1970s. Hypertension and obesity are both significant risk factors in the development of CVDs. Together hypertension and obesity act to increase the risk of CVDs. While the association that obesity leads to hypertension and CVDs has been ascertained, physiologically how this occurs is not understood. However, leptin an adipose derived hormone is a likely candidate. Leptin is secreted from adipose tissue in proportion to the amount of adipose tissue an animal possesses. Hence in obesity plasma leptin levels are substantially elevated. Leptin acts in the hypothalamus and physiologically causes a decrease in food intake while stimulating energy expenditure, via the SNS. This thesis addresses the adverse actions obesity has on metabolic diseases, and specifically the role leptin has on cardiovascular regulation.