Ghrelin in the CNS: From hunger to a rewarding and memorable meal?

Olszewski, Pawel K.; Schiöth, Helgi B.; Levine, Allen S.

doi:10.1016/j.brainresrev.2008.01.004

Cited by 54 publications

(31 citation statements)

References 108 publications

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“…Interplay between ghrelin and orexin (Toshinai et al, 2003) suggests that arousal and wakefulness may be required for ghrelin's orexigenic effect (Olszewski et al, 2008). Mice with double knockout (KO) of NPY/AgRP genes completely lack the orexigenic action of ghrelin, confirming that these neuropeptides mediate and are essential for the orexigenic effect of this peptide hormone (Chen et al, 2004).…”

Section: Page 3 Of 44mentioning

confidence: 99%

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

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Section: Page 3 Of 44mentioning

confidence: 99%

Ghrelin in obesity and endocrine diseases

Scerif

Goldstone

Korbonits

2011

Molecular and Cellular Endocrinology

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“…Taken together these studies strongly support a cognition enhancer effect for ghrelin through its hippocampal action. Ghrelin-mediated signaling could provide the link between metabolic requirements, feeding and memory retention, facilitating the successful search for food sources, allowing animals to remember food locations and to retain the successful approach that was used to find them (44,45).…”

Section: Discussionmentioning

confidence: 99%

Ghrelin triggers the synaptic incorporation of AMPA receptors in the hippocampus

Ribeiro

Catarino

Santos

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Ghrelin is a peptide mainly produced by the stomach and released into circulation, affecting energy balance and growth hormone release. These effects are guided largely by the expression of the ghrelin receptor growth hormone secretagogue type 1a (GHS-R1a) in the hypothalamus and pituitary. However, GHS-R1a is expressed in other brain regions, including the hippocampus, where its activation enhances memory retention. Herein we explore the molecular mechanism underlying the action of ghrelin on hippocampal-dependent memory. Our data show that GHS-R1a is localized in the vicinity of hippocampal excitatory synapses, and that its activation increases delivery of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic-type receptors (AMPARs) to synapses, producing functional modifications at excitatory synapses. Moreover, GHS-R1a activation enhances two different paradigms of long-term potentiation in the hippocampus, activates the phosphatidylinositol 3-kinase, and increases GluA1 AMPAR subunit and stargazin phosphorylation. We propose that GHS-R1a activation in the hippocampus enhances excitatory synaptic transmission and synaptic plasticity by regulating AMPAR trafficking. Our study provides insights into mechanisms that may mediate the cognitionenhancing effect of ghrelin, and suggests a possible link between the regulation of energy metabolism and learning.T he appetite-stimulating peptide ghrelin is a 28-aa peptide predominantly produced by X/A-like cells in the oxyntic glands of the stomach as well as in the intestine (1), and secreted into the blood stream. This peptide promotes pituitary growth hormone secretion, through activation of the growth hormone secretagogue type 1a receptor (GHS-R1a) or ghrelin receptor (2). Additionally, ghrelin is involved in the regulation of energy balance by increasing food intake and reducing fat utilization (3). Plasma ghrelin levels rise before meals and decrease thereafter (4), a pattern which is consistent with the implication of ghrelin in preprandial hunger and meal initiation. Ghrelin is secreted into the circulation and crosses the blood-brain barrier (5, 6), but there is also evidence for ghrelin synthesis locally in the brain (2,7,8). The GHS-R1a receptor mRNA was initially found in the hypothalamus and in the pituitary gland (9), and later detected in the hippocampus (10). GHS-R1a is a G protein-coupled seventransmembrane domain receptor (3), which can signal through guanine nucleotide-binding protein (G protein) subunit alpha 11 (Gq class) to activate phosphatidylinositol-specific phospholipase C, generating 1,4,5-triphosphate (IP 3 ) responsible for Ca 2+ intracellular release from endoplasmic reticulum, and diacylglicerol, which in turn activates protein kinase C (PKC) (11). Ghrelin receptor activation is also coupled to the phosphatidylinositol 3 (PI3)-kinase signaling cascade in different cellular systems through a pertussis toxin-sensitive G protein (G i/o α) (11), and to protein kinase A (PKA) in isolated hypothalamic neurons, modulating N-type Ca 2+ channels (12).T...

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“…not preference learning (172). Ghrelin is one gut hormone that stimulates feeding and is implicated in food reward (149,165), but glucose acts in the intestine to suppress ghrelin release (260), which seems inconsistent with a ghrelin role in glucosestimulated intake and flavor conditioning. Insulin has been suggested to be a humoral signal for postoral glucose reward (249).…”

Section: Oral and Postoral Carbohydrate Sensing And Preferencementioning

confidence: 99%

Role of gut nutrient sensing in stimulating appetite and conditioning food preferences

Sclafani

Ackroff

2012

American Journal of Physiology-Regulatory, Integrative and Comp

166

186

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The discovery of taste and nutrient receptors (chemosensors) in the gut has led to intensive research on their functions. Whereas oral sugar, fat, and umami taste receptors stimulate nutrient appetite, these and other chemosensors in the gut have been linked to digestive, metabolic, and satiating effects that influence nutrient utilization and inhibit appetite. Gut chemosensors may have an additional function as well: to provide positive feedback signals that condition food preferences and stimulate appetite. The postoral stimulatory actions of nutrients are documented by flavor preference conditioning and appetite stimulation produced by gastric and intestinal infusions of carbohydrate, fat, and protein. Recent findings suggest an upper intestinal site of action, although postabsorptive nutrient actions may contribute to flavor preference learning. The gut chemosensors that generate nutrient conditioning signals remain to be identified; some have been excluded, including sweet (T1R3) and fatty acid (CD36) sensors. The gut-brain signaling pathways (neural, hormonal) are incompletely understood, although vagal afferents are implicated in glutamate conditioning but not carbohydrate or fat conditioning. Brain dopamine reward systems are involved in postoral carbohydrate and fat conditioning but less is known about the reward systems mediating protein/glutamate conditioning. Continued research on the postoral stimulatory actions of nutrients may enhance our understanding of human food preference learning.

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Ghrelin in the CNS: From hunger to a rewarding and memorable meal?

Cited by 54 publications

References 108 publications

Ghrelin in obesity and endocrine diseases

Ghrelin in obesity and endocrine diseases

Ghrelin triggers the synaptic incorporation of AMPA receptors in the hippocampus

Role of gut nutrient sensing in stimulating appetite and conditioning food preferences

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