Hypothalamic κ-opioid receptor modulates the orexigenic effect of ghrelin

Amparo Romero-Picó, Maria J. Vázquez, David González-Touceda, Cintia Folgueira, Karolina P. 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 journalArticlepeer-review

37 Scopus citations


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
Issue number7
StatePublished - Jun 2013

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health


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