Leptin administration increases small intestinal response to cholecystokinin in leptin-deficient obese mice

Abstract

Introduction. Leptin receptors are present in the jejunum, to a lesser degree in the ileum, and also in vagal neurons. Leptin has been shown to increase the duodenal secretion of cholecystokinin (CCK) in rats and to act with CCK on vagal mechanoreceptors in the regulation of small intestinal motility in cats. We have recently demonstrated that leptin-deficient (Lep ob) obese mice have increased jejunal and normal ileal responses to CCK. To confirm that these abnormalities were due to leptin deficiency, we hypothesized that leptin administration would alter the abnormality in small intestinal motility observed in leptin-deficient obese mice. Methods. Twelve-week-old female leptin-deficient (Lep ob) obese mice received daily injections of saline ( n = 12) or 5 μg/g recombinant murine leptin IP ( n = 12). All animals were weighed daily. After 1 month of injections, whole thickness jejunal and ileal longitudinal segments were harvested and mounted in an organ bath. Optimal length and tension were determined by response to acetylcholine (ACh 10 −5 M). Contractile response to CCK 10 −8,−7,−6 M also was measured. Data are expressed as N/cm 2 and were compared by Student’s t-test and two-way ANOVA. Results. Body weights, and jejunal and ileal responses to 10 −5 M ACh and 10 −7 M CCK for both groups are presented below. Conclusions. These data suggest that daily leptin administration for 1 month in leptin-deficient (Lep ob) obese mice (1) increases both jejunal and ileal responses to cholecystokinin and (2) does not alter responses to acetylcholine. Therefore, we conclude that regulation of small intestinal motility may be influenced by the synergistic action of cholecystokinin and leptin. TABLE—ABSTRACT P74 Body Wt (g) Jejunum Ileum ACh CCK ACh CCK Saline 48.9 ± 0.1 532 ± 54 † 174 ± 28 1292 ± 103 211 ± 49 Leptin 33.8 ± 0.1 ∗ 649 ± 51 † 290 ± 50 ∗ 1191 ± 87 352 ± 46 ∗ ∗ P < 0.05 versus Saline; † P < 0.05 versus Ileum.