1. Hypothalamic κ-Opioid Receptor Modulates the Orexigenic Effect of Ghrelin
- Author
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Douglas A. Velásquez, María J. Vázquez, Suzanne L. Dickson, Karolina P. Skibicka, David González-Touceda, Rubén Nogueiras, Amparo Romero-Picó, Roger A.H. Adan, Cintia Folgueira, Margriet A. van Gestel, Mayte Alvarez-Crespo, Herbert Herzog, Christoph Schwarzer, Carlos Dieguez, and Miguel López
- Subjects
Male ,Narcotic Antagonists ,Eating ,0302 clinical medicine ,Opioid receptor ,Agouti-Related Protein ,Drug Interactions ,Neuropeptide Y ,Receptors, Ghrelin ,Receptor ,media_common ,2. Zero hunger ,0303 health sciences ,digestive, oral, and skin physiology ,Intracellular Signaling Peptides and Proteins ,Enkephalins ,Ghrelin ,3. Good health ,Ventral tegmental area ,Psychiatry and Mental health ,Infusions, Intraventricular ,medicine.anatomical_structure ,Original Article ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction ,medicine.drug ,medicine.medical_specialty ,Reinforcement Schedule ,Microinjections ,medicine.drug_class ,media_common.quotation_subject ,Neuropeptide ,Biology ,03 medical and health sciences ,Internal medicine ,Orexigenic ,medicine ,Animals ,Gene Silencing ,Protein Precursors ,030304 developmental biology ,Pharmacology ,Orexins ,Receptors, Opioid, kappa ,Neuropeptides ,Ventral Tegmental Area ,Arcuate Nucleus of Hypothalamus ,Appetite ,Rats ,Endocrinology ,Opioid ,Conditioning, Operant ,030217 neurology & neurosurgery - 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.
- Published
- 2013
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