We report here that RalA gene and protein expression and activity are increased in adipocytes from obese mice and further that targeted deletion of Rala in white, but not brown, adipocytes attenuates HFD-induced obesity, due to dramatically increased energy expenditure and mitochondrial oxidative phosphorylation, specifically in inguinal WAT (iWAT). This evidence concerns the gene RALA and obesity due to melanocortin 4 receptor deficiency.