Targeting the serotonergic pathway in humans to treat metabolic disease

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The number of people who are overweight or obese continues to rise. Obesity is associated with other conditions such as high blood pressure, type 2 diabetes and heart disease. Therefore, new treatments for obesity are urgently required. While most treatments for obesity aim to reduce the amount of food we eat, an alternative approach is to increase the amount of energy we burn. There is a special type of fat tissue in our bodies called brown fat. Brown fat's role is to burn energy to make heat to keep us warm when we are in a cold environment. Developing new treatments to activate brown fat is a new strategy to try to treat obesity and the associated conditions. However, we do not fully understand how brown fat activation is controlled.In this research we are determining how a substance in the body called serotonin controls how brown fat is activated. Serotonin is very important in the brain and controls different processes in the body such as our mood and our appetite. We will recruit healthy volunteers to different studies to test how altering their serotonin levels controls their brown fat activity. We will measure brown fat activity using different techniques such as PET imaging (which we use to see the active brown fat deep in the body), infrared imaging (which measures the heat produced by brown fat) and microdialysis (where we place special tubes in brown fat to measure the substances it uses and produces). We will also determine how serotonin alters energy expenditure by human brown fat cells in culture. By understanding how serotonin controls how much energy we burn, we may be able to identify new treatments for obesity that increase our energy expenditure.