ICV leptin effects on spontaneous physical activity and feeding behavior in rats

Although leptin causes negative energy balance by reducing food intake and increasing energy expenditure, the effect of leptin on spontaneous physical activity (SPA) is not clearly established. To test the hypothesis that leptin enhances SPA in rats, male Sprague-Dawley rats were injected intracerebroventricularly (ICV) with either 10mug of leptin or artificial cerebrospinal fluid (aCSF) before dark onset (12:00h) once daily for 5 successive days. The rats were individually housed in behavioral monitoring cages to measure feeding behavior and SPA throughout the study. Both groups had a diurnal pattern of SPA being low during the light period and high during the dark period. Specifically, there were two peaks of SPA during the dark period, with the first peak taking place around the dark onset and the second occurring approximately 6h towards the light onset. Leptin treatment resulted in a significant increase in SPA whether or not it was expressed in terms of light-dark, daily or diurnal basis. Increased SPA was consistently observed throughout the entire 5-day study in spite of the fact that the rats were consistently eating less and losing body weight. With reduction in weight of fat pads and increase in apoptosis of fat pads but no change in body temperature, leptin decreased size, duration and number of meals without altering eating rate, thereby increasing satiety. Our data show that increased activity is a key determinant in negative energy balance induced by leptin, which cannot be accounted for solely by the leptin-induced food intake reduction.