Metabolic profiling and identification of biomarkers for weight loss

Obesity is a worldwide rising pandemic disease and a great challenge for healthcare systems due to its associated disorders. Exercise, drugs and all sorts of dietary plans are typical weight loss options that overweight or obese individuals are offered besides more radical actions such as bariatric surgery. However, weight loss is sometimes incremental, especially at the very start of a regimen and this often leads to the patient dropping-out of a dietary program. Hence, there is a need to identify biomarkers that are affected over a 24-hour interval and use them to provide quantitative biofeedback on the efficiency of a diet. It would also allow personalised optimisation of dieting parameters with relevance to short-term. There is also a need to understand the effects of various food on these biomarkers and the mechanisms by which the food affects adipose tissue metabolism in particular. This thesis describes for the first time the identification of insulin, lactate and angiotensin converting enzyme (ACE) as potential biomarkers of weight loss. Decreased levels of these biomarkers were observed in the urine of individuals following a low-calorie diet. Importantly, these changes preceded weight loss and were consistently associated with weight loss on the long term. Therefore, insulin, lactate and ACE are biomarkers that may be used to assess the metabolic benefits of a diet in its early stages where weight loss is not always a reliable parameter. Further, nutritional means are identified by which ACE could be regulated and it is found that lemon extract (LE) down regulates ACE activity in adipocytes and is associated with both improved adipose insulin sensitivity and increased lipid mobilization. In a proof of concept study, biomarkers have been identified that could provide molecular feedback on food intake behaviour.