It is well described that obesity and low body weight has a negative influence on survival in normal subjects. Above or below an “optimal” body mass, a person’s lifespan decreases. Similarly, elevated body-mass index may increase a person’s susceptibility to prevalent diseases such as stroke, heart failure, rheumatoid arthritis (RA), and breast or colorectal cancer. However, not all published studies agree on these findings. Moreover, it has been suggested that obesity may improve the prognosis of those patients who suffered these prevalent diseases. This controversy is known as the Obesity Paradox. Since today obesity is a major health problem in Spain and developed countries, it is necessary to develop a therapeutic strategy that allows doctors to care more efficiently to these patients. So, the main objective of this project is to understand the physiopathology and molecular mechanism behind the obesity paradox in order to identify new targets that could be used to improve the overall prognosis of prevalent (stroke, heart failure, RA, and breast/colorectal cancer diseases), beyond obesity populations. Impact of the project: Development of new clinical practice guidelines for obesity management associated to multiple prevalent diseases (stroke, heart failure, RA, and breast/colorectal cancer); Improvement of the effectiveness of technology use in prevention and care of obesity associated to these multiple prevalent diseases; identification of new pathways and/or molecular targets for the development of biomarkers and clinical trials for treat obesity associated to the mentioned diseases. On the other hand, this project meets the characteristics of the call to be a translational research project that focuses on a relevant health problem (obesity-associated prevalent diseases) that accomplishes the research priorities of the AES 2013 call.