Hypothalamic κ-opioid receptor modulates the orexigenic effect of ghrelin

Amparo Romero-Picó, Maria J. Vázquez, David González-Touceda, Cintia Folgueira, Karolina Skibicka, Mayte Alvarez-Crespo, Margriet A. Van Gestel, Douglas A. Velásquez, Christoph Schwarzer, Herbert Herzog, Miguel López, Roger A. Adan, Suzanne L. Dickson, Carlos Diéguez, Rubén Nogueiras

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The opioid system is well recognized as an important regulator of appetite and energy balance. We now hypothesized that the hypothalamic opioid system might modulate the orexigenic effect of ghrelin. Using pharmacological and gene silencing approaches, we demonstrate that ghrelin utilizes a hypothalamic κ-opioid receptor (KOR) pathway to increase food intake in rats. Pharmacological blockade of KOR decreases the acute orexigenic effect of ghrelin. Inhibition of KOR expression in the hypothalamic arcuate nucleus is sufficient to blunt ghrelin-induced food intake. By contrast, the specific inhibition of KOR expression in the ventral tegmental area does not affect central ghrelin-induced feeding. This new pathway is independent of ghrelin-induced AMP-activated protein kinase activation, but modulates the levels of the transcription factors and orexigenic neuropeptides triggered by ghrelin to finally stimulate feeding. Our novel data implicate hypothalamic KOR signaling in the orexigenic action of ghrelin.

Original languageEnglish (US)
Pages (from-to)1296-1307
Number of pages12
JournalNeuropsychopharmacology
Volume38
Issue number7
DOIs
StatePublished - Jun 1 2013

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Ghrelin
Opioid Receptors
Opioid Analgesics
Eating
Pharmacology
Arcuate Nucleus of Hypothalamus
Ventral Tegmental Area
AMP-Activated Protein Kinases
Gene Silencing
Appetite
Neuropeptides
Transcription Factors

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Romero-Picó, A., Vázquez, M. J., González-Touceda, D., Folgueira, C., Skibicka, K., Alvarez-Crespo, M., ... Nogueiras, R. (2013). Hypothalamic κ-opioid receptor modulates the orexigenic effect of ghrelin. Neuropsychopharmacology, 38(7), 1296-1307. https://doi.org/10.1038/npp.2013.28
Romero-Picó, Amparo ; Vázquez, Maria J. ; González-Touceda, David ; Folgueira, Cintia ; Skibicka, Karolina ; Alvarez-Crespo, Mayte ; Van Gestel, Margriet A. ; Velásquez, Douglas A. ; Schwarzer, Christoph ; Herzog, Herbert ; López, Miguel ; Adan, Roger A. ; Dickson, Suzanne L. ; Diéguez, Carlos ; Nogueiras, Rubén. / Hypothalamic κ-opioid receptor modulates the orexigenic effect of ghrelin. In: Neuropsychopharmacology. 2013 ; Vol. 38, No. 7. pp. 1296-1307.
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abstract = "The opioid system is well recognized as an important regulator of appetite and energy balance. We now hypothesized that the hypothalamic opioid system might modulate the orexigenic effect of ghrelin. Using pharmacological and gene silencing approaches, we demonstrate that ghrelin utilizes a hypothalamic κ-opioid receptor (KOR) pathway to increase food intake in rats. Pharmacological blockade of KOR decreases the acute orexigenic effect of ghrelin. Inhibition of KOR expression in the hypothalamic arcuate nucleus is sufficient to blunt ghrelin-induced food intake. By contrast, the specific inhibition of KOR expression in the ventral tegmental area does not affect central ghrelin-induced feeding. This new pathway is independent of ghrelin-induced AMP-activated protein kinase activation, but modulates the levels of the transcription factors and orexigenic neuropeptides triggered by ghrelin to finally stimulate feeding. Our novel data implicate hypothalamic KOR signaling in the orexigenic action of ghrelin.",
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Romero-Picó, A, Vázquez, MJ, González-Touceda, D, Folgueira, C, Skibicka, K, Alvarez-Crespo, M, Van Gestel, MA, Velásquez, DA, Schwarzer, C, Herzog, H, López, M, Adan, RA, Dickson, SL, Diéguez, C & Nogueiras, R 2013, 'Hypothalamic κ-opioid receptor modulates the orexigenic effect of ghrelin', Neuropsychopharmacology, vol. 38, no. 7, pp. 1296-1307. https://doi.org/10.1038/npp.2013.28

Hypothalamic κ-opioid receptor modulates the orexigenic effect of ghrelin. / Romero-Picó, Amparo; Vázquez, Maria J.; González-Touceda, David; Folgueira, Cintia; Skibicka, Karolina; Alvarez-Crespo, Mayte; Van Gestel, Margriet A.; Velásquez, Douglas A.; Schwarzer, Christoph; Herzog, Herbert; López, Miguel; Adan, Roger A.; Dickson, Suzanne L.; Diéguez, Carlos; Nogueiras, Rubén.

In: Neuropsychopharmacology, Vol. 38, No. 7, 01.06.2013, p. 1296-1307.

Research output: Contribution to journalArticle

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T1 - Hypothalamic κ-opioid receptor modulates the orexigenic effect of ghrelin

AU - Romero-Picó, Amparo

AU - Vázquez, Maria J.

AU - González-Touceda, David

AU - Folgueira, Cintia

AU - Skibicka, Karolina

AU - Alvarez-Crespo, Mayte

AU - Van Gestel, Margriet A.

AU - Velásquez, Douglas A.

AU - Schwarzer, Christoph

AU - Herzog, Herbert

AU - López, Miguel

AU - Adan, Roger A.

AU - Dickson, Suzanne L.

AU - Diéguez, Carlos

AU - Nogueiras, Rubén

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N2 - The opioid system is well recognized as an important regulator of appetite and energy balance. We now hypothesized that the hypothalamic opioid system might modulate the orexigenic effect of ghrelin. Using pharmacological and gene silencing approaches, we demonstrate that ghrelin utilizes a hypothalamic κ-opioid receptor (KOR) pathway to increase food intake in rats. Pharmacological blockade of KOR decreases the acute orexigenic effect of ghrelin. Inhibition of KOR expression in the hypothalamic arcuate nucleus is sufficient to blunt ghrelin-induced food intake. By contrast, the specific inhibition of KOR expression in the ventral tegmental area does not affect central ghrelin-induced feeding. This new pathway is independent of ghrelin-induced AMP-activated protein kinase activation, but modulates the levels of the transcription factors and orexigenic neuropeptides triggered by ghrelin to finally stimulate feeding. Our novel data implicate hypothalamic KOR signaling in the orexigenic action of ghrelin.

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Romero-Picó A, Vázquez MJ, González-Touceda D, Folgueira C, Skibicka K, Alvarez-Crespo M et al. Hypothalamic κ-opioid receptor modulates the orexigenic effect of ghrelin. Neuropsychopharmacology. 2013 Jun 1;38(7):1296-1307. https://doi.org/10.1038/npp.2013.28