Role of Xenobiotics in Metabolic Diseases: A Translational Approach

Mennesker blir daglig utsatt for miljøforurensende stoffer som kan påvirke helsen. Vi undersøkte helsemessige konsekvenser av persitente organiske miljøgifter (POPs), som er kjemikalier allestedsnærværende i vår matkjede. Vi fant at overvektige personer med forhøyede nivåer av POP er i høy risiko for kardio metabolske sykdommer sammenlignet med overvektige personer med lave POP nivåer. Videre førte bruken av miljøforurensninger oss til å oppdage en ny biologisk funksjon av fibroblastvækstfaktoren 19 (FGF19), et hormon som utskilles av tarmen. Vi viste at kronisk FGF19 injeksjon øker skjelettmuskulaturmassen i mus og humane muskelceller behandlet med FGF19 blir større enn placebobehandlede humane celler. Vi prøver nå å utvikle et FGF19-basert stoff for å behandle muskelatrofi sykdommer.

The project has contributed to the following: * Advances our understanding of xenobiotics/environmental chemicals and their potential impacts on human health. * Scientific breakthrough about FGF19 and its therapeutic potential again muscle atrophy-linked diseases/disorders. We are now in dialogue with international pharmaceutical companies. * The findings of the project have helped the PI to build his own research team, extend his leadership skills and build up strong international network with leading experts in the field. Taken together, the present project may have important societal impacts in the close future.

Every day, the human body must defend itself against a myriad of potentially noxious xenobiotics (i.e. substances foreign to an entire biological system), and the health consequences of this exposure on our bodies have just begun to be investigated. Insulin resistance is strongly linked to metabolic diseases such as type 2 diabetes, obesity, and cardiovascular diseases. Today, the documented global increase in insulin resistance-related metabolic diseases, together with the poor efficacy of current preventive and therapeutic treatments, means that there is an urgent need to better understand the fundamental causes of insulin resistance. The present proposal represents a new direction that has not previously received much attention, but which is, in fact, pervasive in modern life today: the impact of environmental pollutants on metabolic diseases. TRANSITION is a project designed to radically advance environmental medicine research and renovate our understanding of metabolic diseases. Although t he present proposal can be considered risk-taking because it challenges traditional beliefs about the primary factors involved in contributing to metabolic diseases, my previous and on-going work have provided proof-of-concept for the project's objectives . TRANSITION is expected to not only fill important knowledge gaps in the field, but may also contribute to the development of a novel diagnostic tool that will detect the potential of chemicals to cause metabolic disruptions in humans. To achieve t his, TRANSITION aims to use a translational approach to establish links between in vitro and animal data with the real risks associated with human exposure to pollutants. In a project that bridges basic and applied research, TRANSITION proposes to use a m ulti-disciplinary approach that combines environmental toxicology, molecular biology and physiology, and to use original experimental models as well as a unique human patient study group.