Here we describe two studies: a case control study (MD-Lipolysis) investigating the mechanisms of obesity-driven insulin resistance by combining measurements of circulating levels of metabolites and insulin, adipose tissue lipolysis rates by microdialysis, with adipose tissue genomics; and a cohort study (POEM) to assess the validity of the observed circulating metabolites relation to adiposity and insulin resistance initially found in MD-Lipolysis study. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.