Our second aim was to investigate the ability of TNF-α and hypoxia treatment to establish a long-term model of adipocyte insulin resistance and inflammation, which would allow for the investigation of metabolic cross-talk between obesity-related insulin resistant and inflammatory adipocytes and other cells (e.g. cancer cells, monocytes, myocytes, or hepatocytes) in a co-culture system. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.