Final Report Summary - METABOLISMCONNECT (Can metabolic states induced by diabetes and obesity promote cancer?) Cancer is the second leading cause of death worldwide. An emerging risk factor for cancer is obesity and diabetes. Already today 30% of the liver cancer incidences are associated with obesity and subsequent diabetes. Moreover, obese patients have a 2-5 times increased risk of liver cancer mortality. Unfortunately, current links between obesity and cancer such as increased inflammation can only partially explain this strong correlation and have not led so far to an improved treatment schema for obese liver cancer patients or preventative measures. Thus, there is a pressing need to better understand how obesity increases (liver) cancer risk and mortality rate. Here, we addressed the hypothesis whether metabolism, which is a biological process that is important to sustain cancer proliferation, is the functional interconnection between obesity and liver cancer. To address this hypothesis, we exploited in vivo mouse models (to simulate obese versus lean physiology) and beyond state of the art techniques of metabolomics and 13C tracer analysis, which enables us to determine the in vivo liver metabolism. Using these techniques, we identified strong patterns of metabolic changes in the liver that are induced by obesity and have the potential to be important for liver cancer development and progression. Moreover, we identified a metabolic pathway novel to cancer cells that is associated with obesity. In conclusion, with our work we have increased the understanding of how diet induces liver cancer and we expect that this knowledge will contribute on the long term to an improved cancer treatment and preventative measures in obese patients.This Marie Curie Career Integration Grant support me in establishing an independent research group at the VIB Center for Cancer Biology. The success of my research and my expertise in metabolism (fostered through this grant) allowed a successful integration into VIB and Europe evident from multiple collaborations that resulted in high impact research published for example in Nature and Cell Metabolism. Moreover, my career is progressing as planed as I have advance from a junior PI to a full PI.