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1 Division of Endocrinology/Metabolism, VA Puget Sound Health Care System, Seattle, WA, USA; Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
2 Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
3 Division of Endocrinology/Metabolism, VA Puget Sound Health Care System, Seattle, WA, USA; Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA; Department of Biological Structure, University of Washington School of Medicine, Seattle, WA, USA
* To whom correspondence should be addressed. E-mail: jeblevin{at}u.washington.edu.
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 anorexic dose of leptin administered into the third ventricle (3V) increased by two-fold 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 0.5-4 hr 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 prior to 3V leptin and i.p. 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-hr 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.
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