Hypothalamic κ-Opioid Receptor Modulates the Orexigenic Effect of Ghrelin.

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.

Vázquez, Maria J (author)
González-Touceda, David (author)
Folgueira, Cintia (author)
Skibicka, Karolina PGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xskika (author)
Alvarez-Crespo, Mayte,1980Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xcrema (author)
Van Gestel, Margriet A (author)
Velásquez, Douglas A (author)
Schwarzer, Christoph (author)
Herzog, Herbert (author)
López, Miguel (author)
Adan, Roger A. H. (author)
Dickson, Suzanne L.,1966Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology(Swepub:gu)xdicsu (author)
Diéguez, Carlos (author)
Nogueiras, Rubén (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för fysiologi (creator_code:org_t)

In:Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology: Springer Science and Business Media LLC38:7, s. 1296-3071740-634X
In:Neuropsychopharmacology: Springer Science and Business Media LLC38:7, s. 1296-3070893-133X

By the author/editor: Romero-Picó, Amp ...; Vázquez, Maria J; González-Touceda ...; Folgueira, Cinti ...; Skibicka, Karoli ...; Alvarez-Crespo, ...; show more...; Van Gestel, Marg ...; Velásquez, Dougl ...; Schwarzer, Chris ...; Herzog, Herbert; López, Miguel; Adan, Roger A. H ...; Dickson, Suzanne ...; Diéguez, Carlos; Nogueiras, Rubén; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

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