Treadmill training or caloric restriction delays aging-associated increase in urocortin 2-induced hyperthermia in middle-aged male Wistar rats

Age-related obesity is a growing healthcare burden. Effectiveness of body weight reducing mediators changes with aging and these alterations may contribute to aging obesity. Our previous results suggested a potential contributions of urocortin 2 (UCN2) to aging obesity and age-related cachexia. Lifestyle interventions, such as caloric restriction or physical activity can improve body weight and body composition. Previous observations suggest that lifestyle interventions may also influence age-associated regulatory changes in energy balance. We aimed to study the effects of a 12-week treadmill training or caloric restriction on the central hypermetabolic responsiveness to UCN2 in middle-aged 6- and 12-month old male Wistar rats. Interventions started at age 3- or 9-months. Following the interventions, acute hypermetabolic/hyperthermic responses were tested upon intracerebroventricular injections of UCN2. Both the training and the caloric restriction lead to weight loss and training led to favorable body composition changes. UCN2-induced hypermetabolism/hyperthermia was diminished by both interventions in both age-groups. The Ucn2 mRNA expression detected by RNAscope in situ hybridization in the hypothalamic paraventricular nucleus was also decreased by both interventions. UCN2-induced hypermetabolism/hyperthermia in the trained and caloric restricted middle-aged groups resembled those of young adult 3-month rats. Lifestyle interventions appear to delay age-related regulatory alterations of energy balance.