The Role of Ghrelin in Regulating Synaptic Function and Plasticity of Feeding-Associated Circuits

Serrenho, Débora Vanessa Lourenço; Santos, Sandra D.; Carvalho, Ana Luı́sa

doi:10.3389/fncel.2019.00205

Cited by 53 publications

(32 citation statements)

References 120 publications

(173 reference statements)

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“…Circulating levels of orexigenic hormones such as AG alter appetite and food intake and modulates brain activity within both homeostatic and reward-related brain regions [22]. Serum levels of ghrelin typically rise in the pre-prandial state and fall in the postprandial state—reflecting the hunger and satiety that precedes and follows eating.…”

Section: Discussionmentioning

confidence: 99%

Similarities in Metabolic Flexibility and Hunger Hormone Ghrelin Exist between FTO Gene Variants in Response to an Acute Dietary Challenge

2019

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The rs9939609 polymorphism of the fat mass and obesity-associated (FTO) gene has been associated with obesity, and studies have also shown that environmental/lifestyle interaction such as dietary intake might mediate this effect. The current study investigates the postprandial hormonal regulators of hunger and indirect markers of substrate utilisation and metabolic flexibility following a dietary challenge to determine if suppression of circulating ghrelin levels and/or reduced metabolic flexibility exist between FTO genotypes. One hundred and forty seven healthy, sedentary males and females (29.0 ± 0.7 yrs; 70.2 ± 1.1 kg; 169.1 ± 0.8 cm; 24.5 ± 0.3 kg/m2) complete a single experimental session. Anthropometric measures, circulating levels of active ghrelin, insulin and glucose, and substrate oxidation via indirect calorimetry, are measured pre-prandial and/or post-prandial. The FTO rs9939609 variant is genotyped using a real-time polymerase chain reaction. Metabolic flexibility (∆RER) is similar between FTO genotypes of the rs9939609 (T > A) polymorphism (p > 0.05). No differences in pre-prandial and/or postprandial substrate oxidation, plasma glucose, serum insulin or ghrelin are observed between genotypes (p > 0.05). These observations are independent of body mass index and gender. Altered postprandial responses in hunger hormones and metabolic flexibility may not be a mechanism by which FTO is associated with higher BMI and obesity in healthy, normal-weighted individuals.

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Section: Discussionmentioning

confidence: 99%

Similarities in Metabolic Flexibility and Hunger Hormone Ghrelin Exist between FTO Gene Variants in Response to an Acute Dietary Challenge

2019

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“…Ghrelin, an octanoylated 28-amino acid peptide secreted mainly by the stomach, is the endogenous ligand of the growth hormone secretagogues receptor 1 a (GHS-R1a). Its administration increases not only GH secretion but also food intake and body weight in animals and humans [67][68][69]. Ghrelin effectively prevents muscle atrophy induced by dexamethasone and angiotensin II [70,71].…”

Section: Ghrelinmentioning

confidence: 99%

Cisplatin-Induced Skeletal Muscle Dysfunction: Mechanisms and Counteracting Therapeutic Strategies

Conte

Bresciani

Rizzi

et al. 2020

IJMS

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Among the severe side effects induced by cisplatin chemotherapy, muscle wasting is the most relevant one. This effect is a major cause for a clinical decline of cancer patients, since it is a negative predictor of treatment outcome and associated to increased mortality. However, despite its toxicity even at low doses, cisplatin remains the first-line therapy for several types of solid tumors. Thus, effective pharmacological treatments counteracting or minimizing cisplatin-induced muscle wasting are urgently needed. The dissection of the molecular pathways responsible for cisplatin-induced muscle dysfunction gives the possibility to identify novel promising therapeutic targets. In this context, the use of animal model of cisplatin-induced cachexia is very useful. Here, we report an update of the most relevant researches on the mechanisms underlying cisplatin-induced muscle wasting and on the most promising potential therapeutic options to preserve muscle mass and function.

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“…Further, the midbrain GHS-R1As, co-localized with dopaminergic and cholinergic receptors [ 35 , 36 ], activate the cholinergic–dopaminergic reward link and trigger the VTA dopaminergic signalling, which can be blocked by intra-VTA administration of nicotinic cholinergic and glutamatergic receptor antagonists [ 37 , 38 , 66 ]. Also, GHS-R1A is known to modulate synaptic plasticity in the brain [ 67 , 68 ]. The GHS-R1As are also expressed on the GABA VTA neurones [ 67 ] however, the ghrelin-induced activation of VTA dopamine neurons was not blocked in presence of GABA-A antagonist [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Also, GHS-R1A is known to modulate synaptic plasticity in the brain [ 67 , 68 ]. The GHS-R1As are also expressed on the GABA VTA neurones [ 67 ] however, the ghrelin-induced activation of VTA dopamine neurons was not blocked in presence of GABA-A antagonist [ 39 ]. The CB1Rs and the GHS-R1As are evenly expressed in both the VTA and the NAC and also in hypothalamus.…”

Section: Discussionmentioning

confidence: 99%

“…The CB1Rs and the GHS-R1As are evenly expressed in both the VTA and the NAC and also in hypothalamus. Substantial functional cooperation between the ghrelin and cannabinoid systems in regulation of food intake has been mentioned above [ 27 , 28 , 29 , 30 , 67 ]. Dimerization between CB1R and GHS-R1A has not been directly examined yet, but it was suggested [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

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Alterations in Rat Accumbens Dopamine, Endocannabinoids and GABA Content During WIN55,212-2 Treatment: The Role of Ghrelin

Charalambous

Lapka

Havlickova

et al. 2020

IJMS

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The endocannabinoid/CB1R system as well as the central ghrelin signalling with its growth hormone secretagogoue receptors (GHS-R1A) are importantly involved in food intake and reward/reinforcement processing and show distinct overlaps in distribution within the relevant brain regions including the hypothalamus (food intake), the ventral tegmental area (VTA) and the nucleus accumbens (NAC) (reward/reinforcement). The significant mutual interaction between these systems in food intake has been documented; however, the possible role of ghrelin/GHS-R1A in the cannabinoid reinforcement effects and addiction remain unclear. Therefore, the principal aim of the present study was to investigate whether pretreatment with GHS-R1A antagonist/JMV2959 could reduce the CB1R agonist/WIN55,212-2–induced dopamine efflux in the nucleus accumbens shell (NACSh), which is considered a crucial trigger impulse of the addiction process. The synthetic aminoalklylindol cannabinoid WIN55,212-2 administration into the posterior VTA induced significant accumbens dopamine release, which was significantly reduced by the 3 mg/kg i.p. JMV2959 pretreatment. Simultaneously, the cannabinoid-increased accumbens dopamine metabolic turnover was significantly augmented by the JMV2959 pretreament. The intracerebral WIN55,212-2 administration also increased the endocannabinoid arachidonoylethanolamide/anandamide and the 2-arachidonoylglycerol/2-AG extracellular levels in the NACSh, which was moderately but significantly attenuated by the JMV2959 pretreatment. Moreover, the cannabinoid-induced decrease in accumbens γ-aminobutyric acid/gamma-aminobutyric acid levels was reversed by the JMV2959 pretreatment. The behavioural study in the LABORAS cage showed that 3 mg/kg JMV2959 pretreatment also significantly reduced the systemic WIN55,212-2-induced behavioural stimulation. Our results demonstrate that the ghrelin/GHS-R1A system significantly participates in the rewarding/reinforcing effects of the cannabinoid/CB1 agonist that are involved in cannabinoid addiction processing.

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The Role of Ghrelin in Regulating Synaptic Function and Plasticity of Feeding-Associated Circuits

Cited by 53 publications

References 120 publications

Similarities in Metabolic Flexibility and Hunger Hormone Ghrelin Exist between FTO Gene Variants in Response to an Acute Dietary Challenge

Similarities in Metabolic Flexibility and Hunger Hormone Ghrelin Exist between FTO Gene Variants in Response to an Acute Dietary Challenge

Cisplatin-Induced Skeletal Muscle Dysfunction: Mechanisms and Counteracting Therapeutic Strategies

Alterations in Rat Accumbens Dopamine, Endocannabinoids and GABA Content During WIN55,212-2 Treatment: The Role of Ghrelin

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