Hypothalamic κ-Opioid Receptor Modulates the Orexigenic Effect of Ghrelin.
Romero-Picó A, Vázquez MJ, González-Touceda D, Folgueira C, Skibicka KP, Alvarez-Crespo M, Van Gestel MA, Velásquez DA, Schwarzer C, Herzog H, López M, Adan RA, Dickson SL, Diéguez C, Nogueiras R.
Neuropsychopharmacology. 2013 Jun;38(7):1296-307. doi: 10.1038/npp.2013.28. Epub 2013 Jan 24. PMID: 23348063
Research from Santiago de Compostela team and NeuroFAST collaborators, published in Neuropsychopharmacology (2013), identify a novel pathway that modulates the acute orexigenic effect of ghrelin in hypothalamus. The central opioid system is recognized as an important regulator of addiction behaviors within the mesolimbic system - including food intake - although the molecular mechanisms responsible of food consumption are unclear. Interestingly, as demonstrate in this study, ghrelin uses the kappa opioid receptor system to modulate hypothalamic ghrelin-induce food intake. Pharmacological and genetic ablation of kappa opioid receptor in the arcuate nucleus is sufficient to reduce food intake induced by central ghrelin administration. This finding is the first evidence of kappa opioid receptor system as modulator of homeostatic mechanisms governing food intake regulation, and provides new targets to design anti-obesity drugs.
Central manipulation of dopamine receptors attenuates the orexigenic action of ghrelin.
Romero-Picó A, Novelle MG, Folgueira C, López M, Nogueiras R, Diéguez C.
Psychopharmacology (Berl). 2013 Apr 28. [Epub ahead of print]
Research from Santiago de Compostela team, published in Psychopharmacology (April 2013), demonstrates that modulation of dopamine receptors (D1, D2/D3) interacts with ghrelin-induced food intake. Previous studies suggest that ghrelin, a peptidic hormone stimulating food intake, interacts with the dopamine signaling. However, it is not known whether the orexigenic action of ghrelin is modulated by changes in central dopamine receptors. Central blockade of dopamine receptors by high doses of dopamine receptors antagonists reduce the orexigenic action of ghrelin. Interesting, activation of D1 or D2/3 receptors also causes a significant decrease in ghrelin-induced food intake. This effect is more significant with the co-stimulation of all three receptors. This study reveals the important role that dopamine receptors play on acute stimulation of feeding behavior induced by central administration of ghrelin and contributes to design proper drugs for obesity treatment.
Heterozygous deficiency of endoglin decreases insulin and hepatic triglyceride levels during high fat diet.
Beiroa D, Romero-Picó A, Langa C, Bernabeu C, López M, López-Novoa JM, Nogueiras R, Diéguez C.
PLoS One. 2013;8(1):e54591. doi: 10.1371/journal.pone.0054591. Epub 2013 Jan 15.
Research from Santiago de Compostela team, published in PLOS One (January 2013), explored the role of Endoglin on energy balance and glucose metabolism. Endoglin is a transmembrane auxiliary receptor for transforming growth factor-beta (TGF-beta). Endoglin modulates processes mainly related to vascular physiology and pathophysiology. In addition, its deficiency is related to endothelial dysfunction and there is a clear association between endothelial dysfunction and alterations in glucose metabolism or metabolic syndrome. Heterozygous endoglin deficiency in mice (Eng+/-) decreases high fat diet-induced hepatic triglyceride content and insulin levels. These effects are independent of changes in body weight or adiposity. This study is important because is the first one aimed to investigate the metabolic phenotype of Eng+/- mice in normal conditions or when challenged with high fat diet, and identify Engoglin as a potentially important physiological mediator of metabolism.