Franny Jongbloed

15 1 GENERAL INTRODUCTION & AIMS AND OUTLINE OF THIS THESIS restriction (PR). In chapter 5 , we took a step further and studied the role of the building blocks of proteins, i.e. the essential amino acids leucine, tryptophan and methionine, on postoperative and transcriptional outcome after IRI of the liver. To further understand the role of DR on surgical outcome, in chapter 6 we used a human model that is the opposite of nutrient deprivation, i.e. morbid obesity, followed by a surgical form of DR, namely bariatric surgery. We investigated the detrimental effects of the metabolic syndrome on aging in morbidly obese patients. In particular, we examined the aging of the immune system and whether bariatric surgery is able to reverse these detrimental effects. We took blood samples of morbidly obese patients before and after bariatric surgery and measured relative telomere length and T-cell differentiation status, which are markers of cellular aging. In chapter 7 , a first step towards translation of short-term DR to humans was made by investigating the safety, feasibility of and compliance to a combined DR and PR diet in humans awaiting surgery. Healthy living kidney donors and morbidly obese bariatric surgery patients were offered a synthetic diet containing both DR and PR, or a synthetic placebo-diet that was isocaloric to the individual daily energy requirements. Effects of these diets were compared to those of a control group including donors whom were allowed to eat ad libitum, and were asked to fill in a diary of their nutritional intake. Safety, feasibility and compliance were tested via objective markers in blood samples, as well as subjective outcome in the form of questionnaires filled in before and after the application of the three dietary interventions. Since the DR and PR synthetic diet was considered safe and feasible, in chapter 8 , the effects of this diet on clinical outcome as well as molecular changes was investigated in healthy living kidney donors and their kidney transplant recipients. This was done by examining kidney function and systemic inflammation markers in blood samples taken before, during and after surgery in both kidney donor and recipient. Effects on gene expression profiles were examined in kidney biopsies taken during surgery. In chapter 9 , a summary and discussion of the results described in this thesis are presented and emphasis is put on future perspectives of the research of DR in both the preclinical and clinical setting.