Exendin-4 antagonizes the metabolic action of acylated ghrelinergic signaling in the hypothalamic paraventricular nucleus

Abtahi, Shayan; Howell, Erin; Salvucci, Jack T.; Bastacky, Joshua M.R.; Dunn, David P.; Currie, Paul J.

doi:10.1016/j.ygcen.2018.10.008

Cited by 12 publications

(16 citation statements)

References 86 publications

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“…Intra‐PVN administration of ghrelin also inhibits sympathetic projections to the brown adipose tissue . Moreover, intra‐PVN administration of ghrelin increases the respiratory exchange ratio, indicating that the metabolic pathways are changed in favor of the use of carbohydrates rather than fat . Together, these responses possibly contribute to the increased adiposity after ghrelin administration.…”

Section: The Pvn As a Mediator Of The Action Of Ghrelin On Energy Balmentioning

confidence: 99%

“…Together, these responses possibly contribute to the increased adiposity after ghrelin administration. The effect of ghrelin on metabolism is prevented by a previous peripheral or intra‐PVN administration of the GLP‐1 analogue exendin‐4, suggesting that GLP‐1 may influence similar circuits involved in the control of metabolism. The effects of ghrelin on respiratory exchange ratio are also reversed by pretreatment with urocortin I, serotonin, or 5‐HT2A/2C receptor agonists, which suggests that these neurotransmitters modulate this response.…”

Section: The Pvn As a Mediator Of The Action Of Ghrelin On Energy Balmentioning

confidence: 99%

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The actions of ghrelin in the paraventricular nucleus: energy balance and neuroendocrine implications

Dos‐Santos

Reis

Perelló³

et al. 2019

Annals of the New York Academy of Sciences

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Ghrelin is a peptide mainly produced and secreted by the stomach. Since its discovery, the impact of ghrelin on the regulation of food intake has been the most studied function of this hormone; however, ghrelin affects a wide range of physiological systems, many of which are controlled by the hypothalamic paraventricular nucleus (PVN). Several pathways may mediate the effects of ghrelin on PVN neurons, such as direct or indirect effects mediated by circumventricular organs and/or the arcuate nucleus. The ghrelin receptor is expressed in PVN neurons, and the peripheral or intracerebroventricular administration of ghrelin affects PVN neuronal activity. Intra-PVN application of ghrelin increases food intake and decreases fat oxidation, which chronically contribute to the increased adiposity. Additionally, ghrelin modulates the neuroendocrine axes controlled by the PVN, increasing the release of vasopressin and oxytocin by magnocellular neurons and corticotropin-releasing hormone by neuroendocrine parvocellular neurons, while possibly inhibiting the release of thyrotropin-releasing hormone. Thus, the PVN is an important target for the actions of ghrelin. Our review discusses the mechanisms of ghrelin actions in the PVN, and its potential implications for energy balance, neuroendocrine, and integrative physiological control.

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Section: The Pvn As a Mediator Of The Action Of Ghrelin On Energy Balmentioning

confidence: 99%

Section: The Pvn As a Mediator Of The Action Of Ghrelin On Energy Balmentioning

confidence: 99%

The actions of ghrelin in the paraventricular nucleus: energy balance and neuroendocrine implications

Dos‐Santos

Reis

Perelló³

et al. 2019

Annals of the New York Academy of Sciences

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show abstract

“…Central activation of GLP-1 receptors in the LH and PVN has been found to significantly reduce food intake in rats [ 18 , 19 ]. Furthermore, GLP-1R signaling in the ArcN and PVN via treatment with the GLP-1 receptor agonist, exendin-4 (Ex-4), decreases metabolism and attenuates ghrelin-stimulated increases in metabolic activity [ 20 , 21 ]. Together, these findings suggest that GLP-1 analogues have an anorexigenic effect when administered into the hypothalamus.…”

Section: Introductionmentioning

confidence: 99%

Brain Site-Specific Inhibitory Effects of the GLP-1 Analogue Exendin-4 on Alcohol Intake and Operant Responding for Palatable Food

Colvin

Killen

et al. 2020

IJMS

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Approximately 14.4 million Americans are experiencing alcohol use disorder (AUD) and about two-thirds of people who experience drug addiction will relapse, highlighting the need to develop novel and effective treatments. Glucagon-like peptide-1 (GLP-1) is a peptide hormone implicated in the mesocorticolimbic reward system and has become a peptide of interest with respect to its putative inhibitory effects on drug reward. In order to further develop treatments for those diagnosed with AUD, the interplay between GLP-1 receptor signaling and ethanol consumption must be elucidated. In the present study, we investigated the ability of the GLP-1 analogue, exendin-4 (Ex-4), to alter alcohol intake and operant responding for sucrose pellets in order to further understand the role of this compound in mediating reward. We selected multiple sites throughout the prosencephalic and mesencephalic regions of the brain, where we directly administered various doses of Ex-4 to male Sprague Dawley rats. In alcohol investigations, we utilized a two-bottle choice intermittent access protocol. In separate groups of rats, we adopted an operant paradigm in order to examine the effect of Ex-4 on motivated responding for palatable food. Results indicated that GLP-1 receptor signaling effectively suppressed voluntary alcohol intake when injected into the ventral tegmental area (VTA), the accumbens core (NAcC) and shell (NAcS), the dorsomedial hippocampus (DMHipp), and the lateral hypothalamus (LH), which are all structures linked to brain reward mechanisms. The arcuate nucleus (ARcN) and the paraventricular nucleus (PVN) of the hypothalamus were unresponsive, as was the basolateral amygdala (BLA). However, Ex-4 treatment into the ArcN and PVN suppressed operant responding for sucrose pellets. In fact, the VTA, NAcC, NAcS, LH, and the DMHipp all showed comparable suppression of sucrose responding. Overall, our findings suggest that these central structures are implicated in brain reward circuitry, including alcohol and appetitive motivation, which may be mediated by GLP-1 receptor mechanisms. GLP-1, therefore, may play a critical role in modifying addictive behaviors via activation of multiple GLP-1 systems throughout the brain.

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“…Further, ghrelin, known as a hormone for regulation of motivation and reward system among brain function, has been interacted with GLP-1 and the monoamine transmitter 5-HT (Currie et al, 2010;Abtahi et al, 2019).…”

Section: Resveratrol and Glp-1mentioning

confidence: 99%

Resveratrol Modulates the Gut-Brain Axis: Focus on Glucagon-Like Peptide-1, 5-HT, and Gut Microbiota

Chung

Jeong

Song

2020

Front. Aging Neurosci.

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Resveratrol is a natural polyphenol that has anti-aging and anti-inflammatory properties against stress condition. It is reported that resveratrol has beneficial functions in various metabolic and central nervous system (CNS) diseases, such as obesity, diabetes, depression, and dementia. Recently, many researchers have emphasized the connection between the brain and gut, called the gut–brain axis, for treating both CNS neuropathologies and gastrointestinal diseases. Based on previous findings, resveratrol is involved in glucagon-like peptide 1 (GLP-1) secreted by intestine L cells, the patterns of microbiome in the intestine, the 5-hydroxytryptamine (5-HT) level, and CNS inflammation. Here, we review recent evidences concerning the relevance and regulatory function of resveratrol in the gut–brain axis from various perspectives. Here, we highlight the necessity for further study on resveratrol's specific mechanism in the gut–brain axis. We present the potential of resveratrol as a natural therapeutic substance for treating both neuropathology and gastrointestinal dysfunction.

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Exendin-4 antagonizes the metabolic action of acylated ghrelinergic signaling in the hypothalamic paraventricular nucleus

Cited by 12 publications

References 86 publications

The actions of ghrelin in the paraventricular nucleus: energy balance and neuroendocrine implications

The actions of ghrelin in the paraventricular nucleus: energy balance and neuroendocrine implications

Brain Site-Specific Inhibitory Effects of the GLP-1 Analogue Exendin-4 on Alcohol Intake and Operant Responding for Palatable Food

Resveratrol Modulates the Gut-Brain Axis: Focus on Glucagon-Like Peptide-1, 5-HT, and Gut Microbiota

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