Feeding Behavior and Body Weight Development:: Lessons from Rats
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Background and aim Strains of rats in use today are derived almost exclusively from the Norway rat. Common outbred stocks are Wistar, Long-Evans and Sprague-Dawley, which are believed to better mimic the diverse genetics of human populations. The rat is often the model of choice for studying physiology, e.g. regulation of body weight development and feeding behavior. Overweight, obesity and their comorbidities have become a major health concern globally. Effective weight management for individuals and groups at risk of developing obesity involves a range of long-term strategies. Weight loss treatments include diets, drugs, physical training, and surgery, namely bariatric or obesity surgery. The current standard for bariatric surgery is gastric bypass. There are common beliefs that gastric bypass induces body weight loss due to a reduced food intake and that high-fat diet induces overweight and obesity because of overnutrition. The principal aim of this thesis is to better understand the physiological mechanisms by which gastric bypass achieves body weight loss and by which high-fat diet induces obesity. Methods Male Sprague-Dawley and Long-Evans rats were used. Gastric bypass was made by anastamosis of the distal esophagus to the proximal jejunum, about 2-3 cm distal to the Treitz ligament in an end-to-side fashion. Gastrectomy was performed by removing the whole stomach followed by joining the esophagus and duodenum end-to-end. A high-fat diet-induced obesity model was achieved by feeding three week old Sprague-Dawley rats a standard high-fat diet (60% fat, 20% protein and 20% carbohydrate). Food intake and feeding behavior were recorded automatically with the Comprehensive Laboratory Animal Monitoring System. Body weight was recorded throughout the studies. Body composition was determined by dual energy X-ray absorptiometry. Energy density in feces was determined using an adiabatic bomb calorimeter. Serum levels of ghrelin and obestatin were determined using radioimmunoassay and A-like cells were analyzed by immunohistochemistry and transmission electron microscopy. Statistical analyses were performed in SPSS version 13.0. Results Gastric bypass suppressed body weight gain in young rats and reduced the body weight in adult rats. Long-Evans and Sprague-Dawley rats that received gastric bypass did not have less food intake than sham-operated controls during daytime or night time, both in short-term and long-term. Gastrectomized rats, had smaller meal size during night time but not daytime, and had less food intake but more drinking activity than the controls. Both gastric bypassed and gastrectomized rats had an unchanged fecal energy density postoperatively. However, they had an increased energy expenditure compared with the controls. Gastric ghrelin and obestatin were removed by gastrectomy but not by gastric bypass. The number of ghrelin-producing A-like cells in the stomach was unchanged one year after gastric bypass. The A-like cells probably contained amine as revealed by immunohistochemistry and electron microscopy. The high-fat diet increased the body weight and total fat mass, which was neither associated with an increased calorie intake per day nor with decreased energy expenditure. However, the obese rats had an altered eating behavior, characterized by both rapid consumption and large meal size. Conclusions The rat studies in this thesis have shown that gastric bypass efficiently reduced body weight, particularly the fat compartment. The gastric bypass-induced body weight loss is unlikely to be caused by early satiety, reduced food intake or malabsorption, but probably by a mechanism involving the regulation of energy expenditure. It is still unclear if gastric ghrelin, obestatin or amine in the A-like cells are involved in this context. Finally, it seems that large meal size, and not overnutrition, is responsible for high-fat dietinduced obesity.
PublisherNorges teknisk-naturvitenskapelige universitet, Det medisinske fakultet, Institutt for kreftforskning og molekylær medisin
SeriesDoktoravhandlinger ved NTNU, 1503-8181; 2008:251
Dissertations at the Faculty of Medicine, 0805-7680; 367