ALTERED KINETICS OF HYPOXIA INDUCED HYPOMETABOLISM IN LEPTIN DEFICIENT MICE

Abstract

Hypoxia has long been shown to rapidly decrease the metabolic rate (MR) in small mammals. This hypometabolic state is primarily related to the reduction in the activity of uncoupling proteins which accounts for more than 80% of the total MR in a rodent. The ability to rapidly change this activity could be a major factor of body weight regulation, taking into account the large proportion of BMR used for non-shivering thermogenesis in a small animal. This could be also be true but on a much longer term basis in large mammals. We compared the kinetics of the metabolic changes during 30 min of 10% hypoxia in 5 leptin deficient mice (ob/ob, 41.7 +/− 0.7 g), in 5 diet induced obese C57bl/6J mice (DIO, 49.6 +/− 0.9 g) and 5 control C57bl/6J mice (c, 21.8 +/− 0.4 g). Gas exchanges were measured using a fast responding calorimetric chamber. We found that 1- The drop in MR was much smaller in the ob/ob 25 +/− 6.2 % vs 48.2 +/−7.4 % in the DIO and 44.1 +/− 3.9 % in the c mice 2- VO2 kinetics were similar in the DIO and c mice but they were dramatically blunted in the ob/ob (VO2 subsides slowly for the 30 minutes before reaching a steady state) 3- c and DIO mice displayed a clear VO2 overshoot at recovery to air, the phenomenon was missing in the ob/ob. In conclusion ob/ob mice have a much slower ability to mobilise non ATP related metabolism when exposed to hypoxia with a large metabolic deficit during recovery. This effect is not related to the obesity per se but to an altered control mechanism of uncoupling protein activity in ob/ob mice.