Effects of intraperitoneal leptin administration of leptin on food intake in rats pretreated with cholecystokinin

Jayesh Patel, Ivor S. Ebenezer

University of Portsmouth, Portsmouth, UK

We have previously demonstrated that i.p. administration of low microgram doses of leptin will produce a short-term decrease in food intake in fasted rats which is dependent on intact ascending vagal afferent nerves, and we have suggest that endogenous leptin, released from the stomach in response to food, may act in a paracrine fashion to stimulate ascending vagal afferents in the abdominal area to signal the brain to produce satiety (Patel et al., 2008). Wang et al. (1997) have shown that the gut hormone cholecystokinin (CCK) can sensitise vagal afferents to leptin. The present study was therefore undertaken to investigate the effects of leptin on food intake in rats pre-treated with a low dose of CCK.

Male Wistar rats (body wt: 250 – 320 g; n=8) were food-deprived for 22h each day in their home cages. During experimental trials, the rats were injected i.p. with either saline (sal) followed 30 min later by leptin vehicle (Veh), sal followed by leptin (10 μg kg-1), CCK (2 μg kg-1) followed by Veh, or CCK (2 μg kg-1) followed by leptin (10 μg kg-1). Immediately after the 2nd injection the rats were placed singly in separate experimental cages with free access to food and water for 120 min and cumulative food intake measured. A repeated measures design was used with each rat receiving all treatments; 3 days separated successive drug trials. At the end of the experiment, the animals were allowed a 7 day ‘dry-out’ period and the experimental procedure described above was repeated except that the dose of leptin used was increased to 25 μg kg-1. The data was analysed by ANOVA and Newman-Keuls post-hoc test.

The results are shown in Figs. 1A and 1B. Both doses of leptin significantly decreased cumulative food intake at 15 and 30 min. The hypophagic effects of CCK (2 μg kg-1) were transient and only apparent during the 1st 15 min. Pre-treatment with CCK did not increase the hypophagia observed with leptin alone during the 15 and 30 min measurement periods. However, pre-treatment with CCK increased the duration of the hypophagic effect of leptin so that cumulative food intake was significantly reduced at 60 min (P<0.05, in each case). These finding suggest that prior exposure to CCK prolongs the suppressant effect of leptin on food intake. It is therefore possible to speculate that both gut CCK and leptin act together to produce satiety.

Fig.1. Effects of CCK (2 μg kg-1) administered 30 min prior to (A) leptin (10 μg kg-1) or (B) leptin (25 μg kg-1. Vertical lines represent + s.e.mean. *P<0.05 **P<0.01

Patel, J.D. et al. (2008) Eur. J. Pharmacol., 593, 68 -72.

Wang, Y.H. et al. (1997) Am. J. Physiol., 273, R833 – R 837.