We were able to show that male global HDAC5-KO mice develop adult-onset obesity starting at 6 months of age, driven by marked reductions in adrenergic-stimulated, ATP-consuming processes such as BAT-thermogenesis, skeletal muscle, WAT and liver calcium and creatine futile cycles as well as WAT-lipolysis and ultimately energy expenditure. This evidence concerns the gene HDAC5 and obesity due to melanocortin 4 receptor deficiency.