Modulation of vagal afferent excitation and reduction of food intake by leptin and cholecystokinin.
The gut-peptide, cholecystokinin (CCK), reduces food intake by acting at CCK-1 receptors on vagal afferent neurons, whereas the feeding effects of the adipokine hormone, leptin, are associated primarily with its action on receptors (ObRb) in the hypothalamus. Recently, however, ObRb mRNA has been reported in vagal afferent neurons, some of which also express CCK-1 receptor, suggesting that leptin, alone or in cooperation with CCK, might activate vagal afferent neurons, and influence food intake via a vagal route. To evaluate these possibilities we have been examining the cellular and behavioral effects of leptin and CCK on vagal afferent neurons. In cultured vagal afferent neurons leptin and CCK evoked short latency, transient depolarizations, often leading to action potentials, and increases in cytosolic calcium. There was a much higher prevalence of CCK and leptin sensitivity amongst cultured vagal afferent neurons that innervate stomach or duodenum than there was in the overall vagal afferent population. Furthermore, almost all leptin-responsive gastric and duodenal vagal afferents also were sensitive to CCK. Leptin, infused into the upper GI tract arterial supply, reduced meal size, and enhanced satiation evoked by CCK. These results indicate that vagal afferent neurons are activated by leptin, and that this activation is likely to participate in meal termination, perhaps by enhancing vagal sensitivity to CCK. Our findings are consistent with the view that leptin and CCK exert their influence on food intake by accessing multiple neural systems (viscerosensory, motivational, affective and motor) at multiple points along the neuroaxis.
Peters
James H
JH
Department of V.C.A.P.P., College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6520, USA.
Simasko
Steven M
SM
Ritter
Robert C
RC
D000344:Afferent Pathways / Q000502:physiology*; D000818:Animals; D001069:Appetite Regulation / Q000502:physiology*; D002766:Cholecystokinin / Q000502:physiology*; D004435:Eating / Q000502:physiology; D041981:Gastrointestinal Tract / Q000294:innervation / Q000502:physiology; D006801:Humans; D020738:Leptin / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D012527:Satiation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology*
D020738:Leptin; D002766:Cholecystokinin