Hypothalamic κ-Opioid Receptor Modulates the Orexigenic Effect of Ghrelin

Romero‐Picó, Amparo; Vázquez, María J.; González-Touceda, David; Folgueira, Cintia; Skibicka, Karolina P.; Álvarez-Crespo, Mayte; Gestel, M A van; Velásquez, Douglas A; Schwarzer, Christoph; Herzog, Herbert; López, Miguel; Adan, Roger A.H.; Dickson, Suzanne L.; Diéguez, Carlos; Nogueiras, Rubén

doi:10.1038/npp.2013.28

Cited by 43 publications

(41 citation statements)

References 47 publications

(60 reference statements)

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“…Interestingly, the converse was true for the VTA delivery of a mu-preferring opioid receptor antagonist, which suppressed the effects of VTA ghrelin on food motivation but not food intake (111). Kappa opioid receptor pathways at the hypothalamic level also appear to be a component of the ghrelin sensitive circuitry that is important for feeding control (112). Collectively, these studies outline the divergence of behaviours (food motivation and food intake), involving overlapping but also distinct neurochemical pathways.…”

Section: Neuronal Circuits Mediating the Effects Of Ghrelin On Food Rmentioning

confidence: 95%

Ghrelin Signalling on Food Reward: A Salient Link Between the Gut and the Mesolimbic System

Perelló

Dickson

2015

J Neuroendocrinology

139

117

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.'Hunger is the best spice' is an old and wise saying that acknowledges the fact that almost any food tastes better when we are hungry. The neurobiological underpinnings of this lore include activation of the brain's reward system and the stimulation of this system by the hunger-promoting hormone ghrelin. Ghrelin is produced largely from the stomach and levels are higher preprandially. The ghrelin receptor is expressed in many brain areas important for feeding control, including not only the hypothalamic nuclei involved in energy balance regulation, but also reward-linked areas such as the ventral tegmental area. By targeting the mesoaccumbal dopamine neurones of the ventral tegmental area, ghrelin recruits pathways important for food reward-related behaviours that show overlap with but are also distinct from those important for food intake. We review a variety of studies that support the notion that ghrelin signalling at the level of the mesolimbic system is one of the key molecular substrates that provides a physiological signal connecting gut and reward pathways.

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Section: Neuronal Circuits Mediating the Effects Of Ghrelin On Food Rmentioning

confidence: 95%

Ghrelin Signalling on Food Reward: A Salient Link Between the Gut and the Mesolimbic System

Perelló

Dickson

2015

J Neuroendocrinology

139

117

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“…Adult (8-10 weeks old) wild type (WT) C57BL6 mice, mutant mice (Oprk1 -/-) that lack functional k-OR subtype 1 (B6.129S2-Oprk1 tm1kff /J, The Jackson Laboratory) (Imbernon et al, 2016;Romero-Picó et al, 2013), were maintained on an ad libitum chow diet in Specific Pathogen Free (SPF) conditions and housed with a 12:12-h light-dark cycle. For surgery, mice were anesthetized by an intraperitoneal injection of 138 mg ketamine/Kg BW + 7 mg xylacine/Kg BW.…”

Section: Animal Procedures and Chemicalsmentioning

confidence: 99%

“…However, there is a general lack of information regarding the interaction with other hypothalamic systems. Opioid receptors are widely expressed within the hypothalamus (Mansour et al, 1994), and we have previously demonstrated that the k-OR system in the ARC is able to modulate the orexigenic effect of ghrelin (Romero-Picó et al, 2013). A potential interaction among MCH and the opioid system to regulate food intake and food addiction was postulated previously (Lopez et al, 2011), but the mechanistic aspects and the specific brain areas where this interaction occurs remain unexplored.…”

Section: Introductionmentioning

confidence: 99%

Melanin-Concentrating Hormone acts through hypothalamic kappa opioid system and p70S6K to stimulate acute food intake

et al. 2018

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Melanin-Concentrating Hormone (MCH) is one of the most relevant orexigenic factors specifically located in the lateral hypothalamic area (LHA), with its physiological relevance demonstrated in studies using several genetically manipulated mice models. However, the central mechanisms controlling MCH-induced hyperphagia remain largely uncharacterized. Here, we show that central injection of MCH in mice deficient for kappa opoid receptor (k-OR) failed to stimulate feeding. To determine the hypothalamic area responsible for this MCH/k-OR interaction, we performed virogenetic studies and found that downregulation of k-OR by adeno-associated viruses (shOprk1-AAV) in LHA, but not in other hypothalamic nuclei, was sufficient to block MCH-induced food intake. Next, we sought to investigate the molecular signaling pathway within the LHA that mediates acute central MCH stimulation of food intake. We found that MCH activates k-OR and that increased levels of phosphorylated extracellular signal regulated kinase (ERK) are associated with downregulation of phospho-S6 Ribosomal Protein. This effect was prevented when a pharmacological inhibitor of k-OR was co-administered with MCH. Finally, the specific activation of the direct upstream regulator of S6 (p70S6K) in the LHA attenuated MCH-stimulated food consumption. Our results reveal that lateral hypothalamic k-OR system modulates the orexigenic action of MCH via the p70S6K/S6 pathway.

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“…Central NPY and opioid system have been identified as well as necessary mediators of reward effects of ghrelin in the mesolimbic VTA (Skibicka, Shirazi, Hansson, & Dickson, ). Likewise, the hypothalamic proDyn/KappaOR pathway (Romero‐Pico et al, ) and lateral septum (Terrill, Wall, Medina, Maske, & Williams, ) also appear to be components of the ghrelin circuitry of feeding motivation. Recently, it has also been demonstrated that the ghrelin pathway could be implicated in learned feeding responses.…”

Section: Eating Beyond Metabolic Needs: the Nonhomeostatic Role Of Pementioning

confidence: 99%

Unravelling the role and mechanism of adipokine and gastrointestinal signals in animal models in the nonhomeostatic control of energy homeostasis: Implications for binge eating disorder

Novelle

Diéguez

2018

Euro Eating Disorders Rev

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Central and peripheral signals regulating energy homeostasis interact tightly with neuronal pathways to modulate the hedonic component of food intake. Dysregulation of these interactions could explain the development of binge eating disorder (BED) and/or obesity and the increasing incidence of food addiction. In this review, we have highlighted the crucial role of peripheral hormones, such as leptin and ghrelin, among others, in these nonhomeostatic pathways. We have also emphasised the relevance of central cannabinoid pathway and lateral hypothalamus, with orexin and melanin‐concentrating hormone neurons, as the critical hub controlling motivation and reward. Throughout the manuscript, we have focused on mechanisms learned from animal models of BED/food addiction in order to understand how these peripheral signals can modulate the motivation to eat. Understanding these mechanisms could help us to develop new treatment options for BED and/or obesity.

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Hypothalamic κ-Opioid Receptor Modulates the Orexigenic Effect of Ghrelin

Cited by 43 publications

References 47 publications

Ghrelin Signalling on Food Reward: A Salient Link Between the Gut and the Mesolimbic System

Ghrelin Signalling on Food Reward: A Salient Link Between the Gut and the Mesolimbic System

Melanin-Concentrating Hormone acts through hypothalamic kappa opioid system and p70S6K to stimulate acute food intake

Unravelling the role and mechanism of adipokine and gastrointestinal signals in animal models in the nonhomeostatic control of energy homeostasis: Implications for binge eating disorder

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