The incidence of obesity and type 2 diabetes (T2D) are inexorably increasing and elevated healthcare costs related to the higher disease-associated morbidity are affecting European and extra-European countries. Obesity is associated with resistance to the action of insulin (called insulin-resistance) in adipocytes, which is thought to be induced by a low-grade inflammation present in the adipose tissue. Bariatric surgery has been described as the most effective treatment for obesity; however, the pursuit of non-invasive strategies to override obesity-induced insulin-resistance, promote weight loss and restoration of glycemic control is highly needed. In this project will be investigated the hypothesis that T cells residing in the visceral adipose tissue (VAT) are endowed with immunological and metabolic properties that are altered in obese patients and that, in turn, induce insulin-resistance in adipocytes. The following specific Objectives will be accomplished during the fellowship: I. Determine identity, metabolic demands and immunological functions of human VAT-T cells in obese patients and lean subjects; II. Assess the metabolic properties of human VAT-T cells in obese patients and lean subjects; III. Target VAT-T cell-mediated mechanisms of insulin-resistance. In this project, clinical expertise on diabetes and competences in tissue-specific T cell immunology will be merged with cutting-edge technologies in the cellular and molecular biology of diabetes as well as active support from a broad network of collaborators in the field of cell metabolism. The proposed research project has the scientific, structural and institutional support to bring new knowledge on T cell metabolic demand and functional properties in human obesity and lead to the discovery of new pathways involved in the induction of insulin-resistance, ultimately fostering advances in the field of Immunometabolism as well as the applicant’s career development.