Voluntary running activity is not sufficient for preventing the obesity of Koletsky (fak/fak) rats.

Abstract

Recent data have demonstrated variability in the degree to which voluntary exercise prevents the hyperphagia and obesity in rodent obesity models. OLETF rats lacking CCK1 receptors and melanocortin-4 receptor knockout mice normalize food intake and body weight when given access to a running wheel, whereas exercise seems to have only minimal effects on the obesity of Zucker fatty (fa/fa) or Koletsky (fak/fak, SHROB) rats both congenitally lacking leptin receptors. To further characterize responses to voluntary exercise in the absence of leptin signaling, we determined food intake, body weight and hypothalamic gene expression in SHROB rats in response to running wheel access. We found that sedentary SHROB rats had increased food intake and body weight as compared to lean rats. SHROB rats did use the running wheel but to a less degree than that demonstrated in other models and this degree of activity did not significantly affect food intake or body weight. When we pair fed SHROB rats to the amounts consumed by lean controls, running activity was increased and overall resulted in body weight loss. This combination also resulted in a decrease in blood glucose levels, but did not significantly alter fat mass. Real-time RT PCR determination revealed that the combination of pair feeding and voluntary exercise resulted in further increased NPY and decreased POMC gene expression in the arcuate nucleus compared to sedentary SHROB rats. Together, these data demonstrated that voluntary exercise is not sufficient for preventing the obesity of SHROB rats. (Supported by DK074269).