Dyremodeller for livsstilsygdomme

Description

‘Life-style diseases' is a term that covers a range of chronic inflammatory and metabolic diseases, which have some etiological basis in human life-style. Metabolic syndrome (MS) is a cluster of related life-style diseases including type 2 diabetes (T2D), atherosclerosis (ATS) and obesity (OB). Other diseases which can be said to be life-style caused are Type 1 diabetes (T1D), rheumatic arthritis (RA) and inflammatory bowel disease (IBD). Even within neurobiology diseases such as autism, depression and schizophrenia are by many considered to have an origin in a chronic inflammatory process. Life-style, primarily poor food and low physical activity, is a predisposing factor, but other key determinants such as genetics and problematic events in early life are also important causative factors for life-style diseases. Examples of early-life predisposing factors are low birth weight, formula feeding, and various fetal inflammatory insults, such as infection with Chlamydia pneumoniae or viruses, acting in concert with genetic and hereditary factors, which might initiate the development of these changes and in turn increase the tendency for disease progression after birth. Therefore, these diseases develop over a life-span, which makes animal models crucial as human studies are often long-term and problematic. Rodents which develop obesity, hyperglycemia and hyperinsulinemia are common as models for T2D and obesity, while the rabbit and the ApoE knock out mouse have been the most popular models for CVD. The mouse with it potential for transgenesis will always be an important tool, and especially within T1D seoectively inbred rodents are still among the most commonly applied models, but comparing human patients with herbivorous species, such as rodents and rabbits, can be difficult, and the high cholesterol/calory diet model in the rabbit is not very comparable to ATS in humans, which is primarily characterised by chronic vascular inflammation. Pigs are true monogastric omnivores which absorb, transport and digest lipids in a manner close to humans, easily accept eating a human diet, and develop spontaneous atherosclerosis with a location and morphology similar to humans. While the main lipoprotein class is VLDL in rabbits and HDL in rodents, it is LDL in both pigs and humans. Pigs express two different phenotypes in relation to MS, i.e. a lean and an obese, they have a practical size for experimental procedures and porcine nutrition shows a high degree of similarity with human nutrition. In our group we attempt to develop a animal models, primarily by controlling early life environment, and we work with both mice and pigs. Animals with obesity and chronic inflammation obviously may have more or less serious welfare problems, and we attempt to include solutions to these as an integrated part of our model development.