The AGE-RAGE signaling pathway, which is now understood to be a key pathway in inflammatory disease pathogenesis (including obesity and diabetes) and natural aging mechanisms, has never been studied in hibernators to date, despite the continued interest in understanding how hibernators are able to emerge from torpor unharmed after repeated bouts of torpor (which involves changes in oxidative metabolism and ROS production), and lead long lives relative to their size. Here, RENBP is linked to obesity due to melanocortin 4 receptor deficiency.