Prolonged postsurgical recovery period and adverse effects of a leptin application in endotoxemic obese rodents.

Aims: Increasing evidence suggests that the adipokine leptin plays a role in modulating immune responses and mediating the link between metabolism and immune system. Obese patients are more susceptible to infections than normal weight individuals. To define the pathophysiological role of leptin during endotoxemia, we examined the effects of leptin on energy metabolism, hemodynamics and quality of life in normal weight and diet-induced obese rats by means of radio-telemetry.

Main Methods: Telemetric-transmitter and a central venous catheter were implanted in male Lewis rats. All animals performed two experiments. First, an intravenous injection of 500μlkg(-1) leptin or vehicle (isotonic saline) was performed. After an infusion time of 30min an i.v. bolus of 0.2ml saline over 1min was injected. In the second phase, infusion of placebo or 500μlkg(-1) leptin and an i.v. bolus injection of 100μlkg(-1)Escherichia coli endotoxin were performed. Mean arterial blood pressure (MAP), locomotor activity and electromyogram were recorded via radio-telemetry. Food and water consumption were assessed daily. Quality of life tests were performed at specific times.

Key Findings: Obese animals displayed a prolonged postsurgical recovery period. No benefit could be observed by exogenous leptin in endotoxemic lean or obese animals regarding nutrition balance and locomotor activity. However, leptin treatment even destabilized MAP in obese endotoxemic animals.

Significance: These data demonstrate the necessity to differentiate between normal weight and obese individuals when targeting novel therapeutic strategies for endotoxemia and point out the body weight dependent postsurgical recovery period.