INSULIN RESISTANCE AND OBESITY The sweet aftertaste of exposure to dietary environmental persistent organic pollutants.

Environmental contaminants bioaccumulating in the seafood web are associated with development of life style diseases like obesity and diabetes. Mice fed a diet added the most prominent persistent organic pollutants (POPs) present in seafood over time have been evaluated for the development of obesity and diabetes. The levels of these contaminants I seafood does not induce obesity or diabetes in mice. Endoplasmatic reticulum (ER) stress is one of the cellular mechanisms behind the development of obesity and diabetes. Exposure of undifferentiated adipocytes and hepatocytes to POPs alone and in combination did not activate ER stress. Analysis of liver from mice exposed to the same environmental contaminants did not reveal activation of ER-stress. The effect of exposure to environmental contaminants over generations by regulating gene expression over generations is now an ongoing collaborational study performed in Canada. Male mice will be fed a diet with a cocktail of the most prominent POPs at a level equal to a 20 years dietary intake of fish. In a breeding set up the effect on obesity and diabetes is now evaluated over the two following generations.

Environmental persistent organic pollutants (POP)s have accumulated in the food web over several decades. POPs can activate several of the mechanisms involved in endoplasmatic reticulum (ER) stress propagation as well as epigenetic changes, underlying mec hanisms of obesity and type 2 diabetes. The mechanisms of POP induced ER stress and epigenetic responses warrant further investigation. Here we will evaluate the effects of chronic exposure of relevant doses of the DDT metabolite DDE, PCB 118 and PCB153 t hat still, although banned in 2001, is present at high levels in the seafood food chain on ER stress and development of obesity and type 2 diabetes. We hypothesize that exposure to the POPs DDE, PCB118 and PCB153 induces epigenetic changes of the genome and accelerates the progression of ER stress, promoting induction and progression of style diseases like obesity and type 2 diabetes. The project aims to: 1) Evaluate the effect of DDE, PCB118 and PCB153 alone and in combination on ER stress in cell lines and primary cell cultures; 2) Identify the interplay between POPs and dietary matrix by evaluating the effect of dietary sugar on the effect of DDE, PCB118 and PCB153 in fish oil on ER stress and the progression of obesity and type 2 diabetes; 3) Identif y effects of DDE on epigenetic hereditary modifications as well as in obesity, type 2 diabetes; 4) Identify the role of POPs deposited in adipose tissue; 5) Evaluate the accumulation of POPs in human adipose tissue collected from patients which have under gone bariatric or routine surgery. The project involves a number of leading scientists from Norway, Denmark and China. The individual collaborators have complementary expertise securing state of the art knowledge within each of the different disciplines needed to successfully carry out this ambitious project. This research alliance will be multidisciplinary and international, and rely on existing projects and collaborations, thereby ensuring a high efficiency.