Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal size.
Hindbrain projections of oxytocin neurons in the parvocellular paraventricular nucleus (pPVN) are hypothesized to transmit leptin signaling from the hypothalamus to the nucleus of the solitary tract (NTS), where satiety signals from the gastrointestinal tract are received. Using immunocytochemistry, we found that an anorectic dose of leptin administered into the third ventricle (3V) increased twofold the number of pPVN oxytocin neurons that expressed Fos. Injections of fluorescent cholera toxin B into the NTS labeled a subset of pPVN oxytocin neurons that expressed Fos in response to 3V leptin. Moreover, 3V administration of an oxytocin receptor antagonist, [d-(CH2)5,Tyr(Me)2,Orn8]-vasotocin (OVT), attenuated the effect of leptin on food intake over a 0.5- to 4-h period (P < 0.05). Furthermore, to determine whether oxytocin contributes to leptin's potentiation of Fos activation within NTS neurons in response to CCK, we counted the number of Fos-positive neurons in the medial NTS (mNTS) after 3V administration of OVT before 3V leptin and intraperitoneal CCK-8 administration. OVT resulted in a significant 37% decrease (P < 0.05) in the potentiating effect of leptin on CCK activation of mNTS neuronal Fos expression. Furthermore, 4V OVT stimulated 2-h food intake by 43% (P < 0.01), whereas 3V OVT at the same dose was ineffective. These findings suggest that release of oxytocin from a descending pPVN-to-NTS pathway contributes to leptin's attenuation of food intake by a mechanism that involves the activation of pPVN oxytocin neurons by leptin, resulting in increased sensitivity of NTS neurons to satiety signals.
Blevins
James E
JE
VA Puget Sound Health Care System, Research Service (151 1660 S. Columbian Wy, Seattle, WA 98108, USA. jeblevin@u.washington.edu
Schwartz
Michael W
MW
Baskin
Denis G
DG
D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D002766:Cholecystokinin / Q000502:physiology; D004435:Eating / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D016762:Genes, fos / Q000235:genetics; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D020738:Leptin / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000502:physiology*; D010121:Oxytocin / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D012528:Satiety Response / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D017552:Solitary Nucleus / Q000502:physiology; D013238:Stereotaxic Techniques
D020738:Leptin; D018045:Receptors, Oxytocin; D010121:Oxytocin; D002766:Cholecystokinin