Leptin increases small intestinal response to cholecystokinin in leptin-deficient obese mice.
BACKGROUND
Leptin receptors are present in the jejunum, ileum, and vagal neurons. Leptin increases duodenal secretion of cholecystokinin (CCK) and acts with CCK on vagal mechanoreceptors in the regulation of small intestinal motility. We have demonstrated that leptin-deficient (Lepob) obese mice have increased jejunal and normal ileal responses to CCK. Therefore, we hypothesized that leptin administration alters small intestinal motility observed in leptin-deficient obese mice.


METHODS
Twelve-week-old female leptin-deficient (Lepob) obese mice received either saline (n=12) or 5 microg/g leptin ip (n=12) injections daily. After 4 weeks, jejunal and ileal segments were harvested, mounted in an organ bath, and reacted with acetylcholine (ACh, 10(-5)M) and CCK (10(-8,-7,-6)M). Data were expressed as N/cm2 and compared by ANOVA and Student's t test.


RESULTS
The average body weights in the leptin-treated group were significantly decreased compared to those of the saline-treated group (34 versus 49 g, P <0.01). Jejunal responses to ACh within each group were significantly decreased (P <0.05) when compared to ileal responses. No significant differences in responses to ACh were observed between groups. Jejunal responses to 10(-7,-6)M CCK in the leptin-treated group were significantly greater than those in the saline-treated group. Ileal responses in the leptin group were similarly increased at all CCK concentrations.


CONCLUSIONS
These data suggest that daily leptin administration for 4 weeks in leptin-deficient (Lepob) obese mice increases jejunal and ileal responses to CCK and does not alter responses to ACh. Therefore, we conclude that regulation of small intestinal motility may be influenced by synergistic action of cholecystokinin and leptin.
Kiely
James M
JM
Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Graewin
Shannon J
SJ
Pitt
Henry A
HA
Swartz-Basile
Deborah A
DA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000528:radiation effects; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007421:Intestine, Small / Q000187:drug effects* / Q000503:physiopathology; D020738:Leptin / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D036361:Peptide Hormones / Q000008:administration & dosage*
D020738:Leptin; D018377:Neurotransmitter Agents; D036361:Peptide Hormones; D002766:Cholecystokinin; D000109:Acetylcholine