Altered intestinal motility in leptin-deficient obese mice.
BACKGROUND
Leptin is produced by adipocytes and causes satiety by regulating hypothalamic neurotransmission and energy expenditure. Leptin functions through the active long form of its receptor, which is expressed throughout the gastrointestinal tract, including the vagal neurons concerned with small intestinal motility. However, the role of leptin in small intestinal motility is poorly understood. Therefore, we hypothesized that leptin-deficient (Lepob) obese mice would have altered small intestinal response to neurotransmitters and transit time.


METHODS
Responses of jejunal and ileal segments from lean control and leptin-deficient obese animals to acetylcholine (ACh) and cholecystokinin (CCK) were determined in an organ bath. In addition, gastric emptying was determined as the amount of gavaged liquid diet remaining in the stomach after 1 h, and intestinal transit time was determined by calculating the geometric center (GC) of passage of a fluorescent-labeled marker.


RESULTS
Leptin deficiency resulted in increased jejunal responses to CCK (P <0.05) and a similar response to ACh compared to lean controls. Also, gastric emptying (97% versus 91%, P <0.001) in obese mice was greater. Overall small intestinal transit (GC) in obese mice was decreased (7.3 versus 8.4, P <0.05) even though proximal transit was increased (5.3 versus 1.5, P <0.06).


CONCLUSIONS
These studies indicate that leptin-deficient (Lepob) obese mice have an increased jejunal response to CCK as well as an increased proximal intestinal transit, but an overall decrease in small intestinal transit.
Kiely
James M
JM
Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Noh
Jae H
JH
Graewin
Shannon J
SJ
Pitt
Henry A
HA
Swartz-Basile
Deborah A
DA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology; D007421:Intestine, Small / Q000187:drug effects; D020738:Leptin / Q000172:deficiency*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009765:Obesity / Q000503:physiopathology*
D020738:Leptin; D018377:Neurotransmitter Agents; D002766:Cholecystokinin; D000109:Acetylcholine