Leptin-induced satiation mediated by abdominal vagal afferents.
Leptin is a hormone secreted into the systemic blood primarily by white adipose tissue. However, leptin also is synthesized and stored by cells in the gastric mucosa. Because gastric mucosal leptin is secreted in response to ingestion of a meal, we hypothesized that it might contribute to satiation (meal termination) by acting on gastrointestinal vagal afferent neurons. To test whether leptin is capable of acutely reducing short-term food intake, we measured consumption of a liquid meal (15% sucrose) following low-dose leptin administration via the celiac artery, which perfuses the upper gastrointestinal tract. Leptin (1, 3, 10 mug) was infused via a chronically implanted, nonocclusive celiac arterial catheter or via a jugular vein catheter with its tip in the right cardiac atrium. Fifteen percent sucrose intake was then measured for 30 min. We found that leptin dose dependently inhibited sucrose intake when infused through the celiac catheter but not when infused into the general circulation via a jugular catheter. Plasma leptin concentrations in the general circulation following celiac arterial or jugular leptin infusions were not significantly different. Celiac arterial leptin infusion did not reduce meal size in vagotomized or capsaicin-treated rats. Finally, we also found that reduction of meal size by celiac leptin infusion was markedly enhanced when coinfused with cholecystokinin, a gastrointestinal satiety peptide whose action depends on vagal afferent neurons. Our results support the hypothesis that leptin contributes to satiation by a mechanism dependent on gastrointestinal vagal afferent innervation of the upper gastrointestinal tract.
Peters
J H
JH
Program in Neuroscience, Dept. of VCAPP, College of Veterinary Medicine, Washington State Univ., Pullman, WA 99164-6520, USA. petersj@vetmed.wsu.edu.
McKay
B M
BM
Simasko
S M
SM
Ritter
R C
RC
D000005:Abdomen / Q000294:innervation*; D000344:Afferent Pathways / Q000502:physiology*; D000792:Angiography; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002445:Celiac Artery; D004435:Eating / Q000187:drug effects; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007601:Jugular Veins; D020738:Leptin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012527:Satiation / Q000502:physiology*; D013395:Sucrose / Q000494:pharmacology; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D020738:Leptin; D013395:Sucrose; D002211:Capsaicin