The effects of peripheral leptin infusion on energy expenditure and adipocyte glucose and fatty acid utilization in rats

Abstract

The method by which leptin reduces body energy by specifically reducing body fat mass is unclear. In this study we measured whole animal energy expenditure and adipose glucose and fatty acid utilization in male Sprague Dawley rats infused peripherally with PBS or 40ug leptin/day. Leptin treated animals showed a reduction in weight and food intake over a four day infusion period during which the respiratory exchange ratio (RER) and energy expenditure were measured. Energy expenditure was higher in leptin treated animals than in pair-fed (PF) controls while RER was significantly decreased in leptin and PF controls suggesting increased fatty acid utilization. After 4 days of infusion fat pad weights were lower in leptin treated and PF rats than controls. Glucose oxidation and incorporation into triglycerides was decreased in both epididymal (Epi) and retroperitoneal (RP) fat cells. Insulin responsiveness was inhibited only in cells from leptin-treated rats. Leptin also inhibited fatty acid oxidation in Epi and RP adipocytes while esterification was decreased only in Epi pads. Glycerol release showed no change in lipolysis. Therefore, the changes in whole animal energy expenditure are consistent with previous reports that leptin increases fatty acid oxidation but changes in adipocyte metabolism suggest that loss of fat is associated with inhibition of glucose utilization rather than increased fatty acid oxidation. Supported by NIH R01DK53903.