A potential role for hypothalamomedullary POMC projections in leptin-induced suppression of food intake

Huiyuan Zheng, Laurel M. Patterson, Christopher J. Rhodes, Gwendolyn W. Louis, Karolina P. Skibicka, Harvey J. Grill, Martin G. Myers, Hans Rudolf Berthoud

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Melanocortin-3/4 receptor ligands administered to the caudal brain stem potently modulate food intake by changing meal size. The origin of the endogenous ligands is unclear, because the arcuate nucleus of the hypothalamus and the nucleus of the solitary tract (NTS) harbor populations of proopiomelanocortin (POMC)-expressing neurons. Here we demonstrate that activation of hypothalamic POMC neurons leads to suppression of food intake and that this suppression is prevented by administration of a melanocortin-3/4 receptor antagonist to the NTS and its vicinity. Bilateral leptin injections into the rat arcuate nucleus produced long-lasting suppression of meal size and total chow intake. These effects were significantly blunted by injection of SHU-9119 into the fourth ventricle, although SHU-9119 increased meal size and food intake during the first, but not the second, 14-h observation period. Leptin effects on meal size and food intake were abolished throughout the 40-h observation period by injection of SHU-9119 into the NTS at a dose that by itself had no effect. Neuron-specific tracing from the arcuate nucleus with a Cre-inducible tract-tracing adenovirus in POMC-Cre mice showed the presence of labeled axons in the NTS. Furthermore, density of α-melanocyte-stimulating hormone-immunoreactive axon profiles throughout the NTS was decreased by ∼70% after complete surgical transection of connections with the forebrain in the chronic decerebrate rat model. The results further support the existence of POMC projections from the hypothalamus to the NTS and suggest that these projections have a functional role in the control of food intake.

Original languageEnglish (US)
Pages (from-to)R720-R728
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume298
Issue number3
DOIs
StatePublished - Mar 1 2010

Fingerprint

Pro-Opiomelanocortin
Leptin
Eating
Arcuate Nucleus of Hypothalamus
Meals
Receptor, Melanocortin, Type 3
Receptor, Melanocortin, Type 4
Neurons
Injections
Axons
Observation
Ligands
Melanocyte-Stimulating Hormones
Fourth Ventricle
Solitary Nucleus
Prosencephalon
Adenoviridae
Hypothalamus
Brain Stem
Population

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Zheng, Huiyuan ; Patterson, Laurel M. ; Rhodes, Christopher J. ; Louis, Gwendolyn W. ; Skibicka, Karolina P. ; Grill, Harvey J. ; Myers, Martin G. ; Berthoud, Hans Rudolf. / A potential role for hypothalamomedullary POMC projections in leptin-induced suppression of food intake. In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology. 2010 ; Vol. 298, No. 3. pp. R720-R728.
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A potential role for hypothalamomedullary POMC projections in leptin-induced suppression of food intake. / Zheng, Huiyuan; Patterson, Laurel M.; Rhodes, Christopher J.; Louis, Gwendolyn W.; Skibicka, Karolina P.; Grill, Harvey J.; Myers, Martin G.; Berthoud, Hans Rudolf.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 298, No. 3, 01.03.2010, p. R720-R728.

Research output: Contribution to journalArticle

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AU - Zheng, Huiyuan

AU - Patterson, Laurel M.

AU - Rhodes, Christopher J.

AU - Louis, Gwendolyn W.

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AU - Myers, Martin G.

AU - Berthoud, Hans Rudolf

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AB - Melanocortin-3/4 receptor ligands administered to the caudal brain stem potently modulate food intake by changing meal size. The origin of the endogenous ligands is unclear, because the arcuate nucleus of the hypothalamus and the nucleus of the solitary tract (NTS) harbor populations of proopiomelanocortin (POMC)-expressing neurons. Here we demonstrate that activation of hypothalamic POMC neurons leads to suppression of food intake and that this suppression is prevented by administration of a melanocortin-3/4 receptor antagonist to the NTS and its vicinity. Bilateral leptin injections into the rat arcuate nucleus produced long-lasting suppression of meal size and total chow intake. These effects were significantly blunted by injection of SHU-9119 into the fourth ventricle, although SHU-9119 increased meal size and food intake during the first, but not the second, 14-h observation period. Leptin effects on meal size and food intake were abolished throughout the 40-h observation period by injection of SHU-9119 into the NTS at a dose that by itself had no effect. Neuron-specific tracing from the arcuate nucleus with a Cre-inducible tract-tracing adenovirus in POMC-Cre mice showed the presence of labeled axons in the NTS. Furthermore, density of α-melanocyte-stimulating hormone-immunoreactive axon profiles throughout the NTS was decreased by ∼70% after complete surgical transection of connections with the forebrain in the chronic decerebrate rat model. The results further support the existence of POMC projections from the hypothalamus to the NTS and suggest that these projections have a functional role in the control of food intake.

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