The general aim of the studies described in this thesis is the effect evaluation of a family-based multidisciplinary cognitive behavioral treatment on several domains related to childhood obesity... Show moreThe general aim of the studies described in this thesis is the effect evaluation of a family-based multidisciplinary cognitive behavioral treatment on several domains related to childhood obesity compared to standard care. The main findings from these studies are a modest long-term reduction of both total and abdominal adiposity accompanied by improved physical fitness, while unchanged adiposity in the untreated controls led to decreased physical fitness and deteriorating insulin sensitivity. In addition, we found significantly impaired health related quality of life in the obese children compared to their normal weight peers. We showed that our multidisciplinary lifestyle treatment improved health related quality of life of the obese children after 1 year. We observed a significantly increased postprandial ghrelin response after the multidisciplinary treatment, but no effect on inflammatory markers, nor on gut hormones PYY and GLP-1. Finally, we propose an alternative for the definition of the metabolic syndrome in children, since the usefulness of its current dichotomous form is questionable. We show that a multivariate prediction model based on the individual components of the metabolic syndrome expressed as standard deviation scores (SDS) has a good predictive value regarding increased HOMA-IR SDS. Show less
Nowadays, obesity has reached epidemic proportions globally. It can lead to several chronic diseases, including insulin resistance/type 2 diabetes mellitus. Feeding behaviour is regulated in the... Show moreNowadays, obesity has reached epidemic proportions globally. It can lead to several chronic diseases, including insulin resistance/type 2 diabetes mellitus. Feeding behaviour is regulated in the hypothalamus of the brain by two opposing pathways: NPY/AgRP neurons vs. POMC/CART neurons. In addition, there are numerous peripheral signals, deriving from stomach, gut, pancreas and adipose tissue, that act on the hypothalamus and thereby contribute to the regulation of food intake. The aim of the studies we have performed, was to investigate the effects of some of these neuropeptides and peripheral signals that affect these neuropeptides, on insulin action. Our experiments showed, that NPY can cause insulin resistance, specifically in the liver. The POMC pathway can improve insulin-mediated glucose disposal and does not affect hepatic insulin sensitivity. Therefore, both pathways are not completely opposing each other’s effects, but seem to have a different tissue-specific effect. Experiments with gut hormones like PYY and ghrelin showed that these hormones affect insulin sensitivity as well. Also leptin, and specifically leptin signalling in the brain, was found to be important for insulin sensitivity. In conclusion, this work showed that neuropeptides/hormones that are involved in the regulation of food intake also affect insulin sensitivity. Show less
