Metabolic rate, organ mass, and mitochondrial proton leak variations in lean and obese rats

The purpose of this study was to determine if differences in metabolic rate between lean and obese strains of rats were associated with differences in proton leak across the inner mitochondrial membrane. Metabolic rates were determined for each of five obese Zucker, Sprague-Dawley, and Fisher 344 rats and three lean Zucker rats by 24-hour indirect respiration calorimetry measurements. Feed intakes were different (P < 0.05) among all strains, with the obese Zucker rats having the greatest intakes. Adjusted to a common dietary intake, the obese Zucker rats had at least 21% lower heat productions than the lean strains of rats. Following the calorimetry measurements, the rats were sacrificed, internal organs were removed and weighed and mitochondria were isolated from the liver. Internal organs composed a larger proportion of lean body mass in obese compared to lean rats. Respiration rates and membrane potentials of the mitochondria were then determined. Proton leak kinetics were visualized by plotting proton leak (calculated from respiration rate) against membrane potential. The lean rats had a 2-3-fold higher proton leak rate than the obese Zucker rats at the same membrane potential. A low mitochondrial proton leak rate may explain part of the abnormal heat productions and bioenergetic efficiencies in the obese Zucker rat.