TY - JOUR
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 P.
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
N1 - Funding Information:
We thank Luz Casas and Ana Senra, at the University of Santiago de Compostela, for helping with in situ hybridization and immunofluorescence techniques. The research leading to these results received funding from the European Community, primarily grant agreement FP7-KBBE-2009-3-245009 (CD, SLD, and RAHA) but also ERC-2011-StG-OBESITY53-281408 (RN), and FP7-KBBE-2010-4-266408. The research was also supported by Ministerio de Educa-cion y Ciencia (CD: BFU2011-02001; ML: RyC-2007-00211; RN: RYC-2008-02219 and SAF2009-07049; Xunta de Galicia (ML: 10PXIB208164PR, RN: 2010/14 and 2012-CP069), Fondo Investigationes Sanitarias (ML: PS09/01880), CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII. SLD was also supported by the Swedish Research Council for Medicine (2009-S266) and FOU/ALF Göteborg (ALFGBG-138741).
PY - 2013/6
Y1 - 2013/6
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.
AB - 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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U2 - 10.1038/npp.2013.28
DO - 10.1038/npp.2013.28
M3 - Article
C2 - 23348063
AN - SCOPUS:84878545056
SN - 0893-133X
VL - 38
SP - 1296
EP - 1307
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 7
ER -