Please activate JavaScript!
Please install Adobe Flash Player, click here for download

GRK 1482 Jahrbuch 2011-2014

Abstract So far, we could not verify the hypothesis, that an impairment of the intestinal barrier due to HFD feeding leads to the gradual development of metabolic diseases like a reduction in glucose tolerance. The glu- cose sensitivity impairment is a quick physiological response to HFD and just persistent in DIO mice suggesting an important contribution of anabolic metabolism of adipocytes. Generating a catabolic state of adipocytes by caloric restriction normalizes glucose tolerance rapidly. All DIO effects seem to be reversible. Introduction It is hypothesized, that high fat diet (HFD) and/or diet-induced obesity (DIO) impair the gut interface as a consequence of inflammatory processes lea- ding to the gradual development of metabolic di- seases (e.g. impaired glucose tolerance). In the literature it is demonstrated that four weeks HFD feeding leads to the translocation of bacteria de- rived lipopolysaccharide (LPS) into plasma. This endotoxemia may be responsible for metabolic changes like weight gain, insulin resistance and hyperglycemia as LPS-injected mice show similar effects [1,2]. However it is not clear whether these inflammatory processes and the DIO lead to an im- pairment of the intestinal barrier or if the HFD itself changes barrier integrity and causes metabolic co- morbidities. To distinguish between the impact of HFD feeding and obesity we perform time courses of the intesti- nal barrier function in vivo and ex vivo, the develop- ment of obesity and of impaired glucose tolerance, insulin response and gene expression analysis in three different mouse strains. Therefore we will use strains with different susceptibility to diet induced obesity: AKR/J and C57BL/6J as DIO prone mice and SWR/J as DIO resistant mice [3]. So we have an additional tool to elucidate whether increased fat/energy intake causes the impaired gut barrier function, or rather the barrier defect is secondary to excess body fat storage. We will further test whether dietary interventions like ca- loric restriction or the quality of dietary fat may have a protective role for the gut barrier function. All intestinal barrier measurements ex vivo are per- formed by Valentina Schüppel and Veronika Müller. In vivo data will be presented here. ASSOCIATED FELLOWS Page 68 | GRK Progress Report 2011-2014 Caroline Kless (M.Sc.) Molecular Nutritional Medicine PhD Metabolic changes by high fat diet and their reversibility in different mouse strains