To examine whether changes in the adipose tissue environment drive metabolic and inflammatory activation of ATMs in obesity, we co-cultured BMDMs with lean or obese adipose tissue for 3 days, removed the adipose tissue and examined the adipose tissue-induced activation of BMDMs in comparison with classically (LPS) or alternatively (IL-4) activated BMDMs both directly (metabolism) and after 24 h in fresh medium (cytokines). This evidence concerns the gene IL4 and obesity due to melanocortin 4 receptor deficiency.