Beside insulin and catecholamines, atrial natriuretic peptide (ANP) is a vital regulator of adipocyte lipolysis. As obesity is characterized by catecholamine resistance, no data are available on ANP sensitivity. The aim of this study was to investigate ex vivo lipolytic sensitivity of subcutaneous (SCAT) and visceral adipose tissue (VAT) for ANP in lean (n=13, BMI=23.9±1.1) and obese subjects (n=28, BMI=38.3±3.8), with or without type 2 diabetes (HbA1c ≥6.5%). Mature adipocytes were isolated and exposed to increasing ANP concentrations. ANP sensitivity was significantly higher in SCAT compared to VAT. Interestingly, maximal lipolytic response to ANP was significantly lower in the SCAT of diabetic obese, compared to lean subjects, accompanied by significantly higher expression of the scavenging type-C ANP receptor. This study shows that ANP regulated adipocyte lipolysis in obese diabetic men is blunted. Therefore, improving ANP sensitivity might be a way to improve body weight control and insulin sensitivity in obesity. ; obesity; adipose tissue; type 2 diabetes mellitus