Negative Modulation of the Metabotropic Glutamate Receptor Type 5 as a Potential Therapeutic Strategy in Obesity and Binge-Like Eating Behavior

Oliveira, Tadeu P. D.; Gonçalves, Bruno Daniel Correia; Oliveira, Bruna S; Oliveira, Antônio Carlos Pinheiro de; Reis, Helton José; Ferreira, Cláudia N.; Aguiar, Daniele C.; Miranda, Aline Silva de; Ribeiro, Fabíola M.; Vieira, Eliane; Palotás, András; Vieira, Luciene Bruno

doi:10.3389/fnins.2021.631311

Cited by 19 publications

(17 citation statements)

References 66 publications

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“…According to our data, mGluR5 did not present changes in IL-4/INF levels in mostly of the tested tissues. However, literatures shows that the negative modulation of mGluR5 by some drugs is able to decrease the transcription of NF-κB in T cell, TNFα, IL-12p70 and INFγ levels in EAT, which may reduce pro-inflammatory responses mediated by these cells 15 , 52 . Moreover, our data indicated that the absence of mGluR5 is associated to a higher IL-10/TNF ratio in the adipose tissue, which may indicate an anti-inflammatory tendency.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, it is found in the cells of innate and adaptive immunity, including macrophages, lymphocytes B and T 16 – 18 . Notably, some studies suggest that this receptor may contribute to fat deposition, metabolic dysfunction, and may also cause a systemic low grade chronic inflammatory state, especially in obesity 14 , 15 , 19 .…”

Section: Introductionmentioning

confidence: 99%

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Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington’s disease

Santos

Ribeiro

Ferreira-Vieira

et al. 2022

Sci Rep

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Obesity represents a global health problem and is characterized by metabolic dysfunctions and a low-grade chronic inflammatory state, which can increase the risk of comorbidities, such as atherosclerosis, diabetes and insulin resistance. Here we tested the hypothesis that the genetic deletion of metabotropic glutamate receptor 5 (mGluR5) may rescue metabolic and inflammatory features present in BACHD mice, a mouse model of Huntington’s disease (HD) with an obese phenotype. For that, we crossed BACHD and mGluR5 knockout mice (mGluR5−/−) in order to obtain the following groups: Wild type (WT), mGluR5−/−, BACHD and BACHD/mGluR5−/− (double mutant mice). Our results showed that the double mutant mice present decreased body weight as compared to BACHD mice in all tested ages and reduced visceral adiposity as compared to BACHD at 6 months of age. Additionally, 12-month-old double mutant mice present increased adipose tissue levels of adiponectin, decreased leptin levels, and increased IL-10/TNF ratio as compared to BACHD mice. Taken together, our preliminary data propose that the absence of mGluR5 reduce weight gain and visceral adiposity in BACHD mice, along with a decrease in the inflammatory state in the visceral adipose tissue (VAT), which may indicate that mGluR5 may play a role in adiposity modulation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington’s disease

Santos

Ribeiro

Ferreira-Vieira

et al. 2022

Sci Rep

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“…In addition, we showed that the genetic deletion of mGluR5 in BACHD mice leads to a reduction in body weight. It has been reported that mGluR5 signaling is a mediator of appetite and energy balance 11,13 . Of note, a previous data showed that the blockade of mGluR5 may decrease anxiety behavior through serotonergic transmission, likely an increase in 5-HT release and the subsequent stimulation of 5-HT 2A/2C receptor 24 .…”

Section: Discussionmentioning

confidence: 99%

“…According to our data, mGluR5 did not present changes in IL-4/INF levels in mostly of the tested tissues. However, literatures shows that the negative modulation of mGluR5 by some drugs is able to decrease the transcription of NF-κB in T cell, TNFα, IL-12p70 and INFγ levels in EAT, which may reduce pro-in ammatory responses mediated by these cells 13,50 . Moreover, our data indicated that the absence of mGluR5 is associated to a higher IL-10/TNF ratio in the adipose tissue, which may indicate an anti-in ammatory tendency.…”

Section: Discussionmentioning

confidence: 99%

“…It is found in the cells of innate and adaptive immunity, including macrophages, lymphocytes B and T [8][9][10] . In this context, some studies suggest that this receptor may contribute to fat deposition, metabolic dysfunction, and may also cause a systemic low grade chronic in ammatory state associated with obesity [11][12][13] . Thus, we designed the present study to test whether the absence of mGluR5 signaling improves metabolic and in ammatory dysfunctions associated to obesity in BACHD mice, a mouse model for Huntington's disease (HD) 14 .…”

Section: Read Full License Introductionmentioning

confidence: 99%

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Metabotropic Glutamate Receptor 5 Knockout Rescues Obesity Phenotype in a Mice Model of Huntington´s Disease

Santos¹,

Ribeiro²,

Vieira³

et al. 2021

Preprint

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Obesity represents a serious global public health problem and is characterized by a low-grade chronic inflammatory state, which can increase the risk of comorbidities, such as: atherosclerosis, diabetes and insulin resistance. In this study, we investigated the effects of the genetic deletion of the metabotropic glutamate receptor 5 (mGluR5) on the modulation of obesity features in BACHD mice, a mouse model of Huntington´s disease. For that, we crossed BACHD and mGluR5 knockout mice (mGluR5−/−) in order to obtain the following groups: Wild type (WT), mGluR5−/−, BACHD and BACHD/mGluR5−/− (double mutant mice). Our results showed that the double mutant mice present decreased body weight as compared to BACHD mice at all tested ages and reduced visceral adiposity as compared to BACHD mice at 6 and 12 months of age. Additionally, 12-month-old double mutant mice present increased adipose tissue levels of adiponectin, decreased leptin levels, and increased IL-10/TNF ratio as compared to BACHD mice. Taken together, our data propose that the absence of mGluR5 reduce weight gain and visceral adiposity in BACHD mice, along with a decrease in the inflammatory state in the visceral adipose tissue (VAT), which may indicate that mGluR5 may play a role in adiposity modulation.

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A suitable model to investigate acute neurological consequences of coronavirus infection

Pimenta,

Da Silva Oliveira,

Lima

et al. 2023

Inflamm. Res.

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Objective and design:The present study aimed to investigate the neurochemical and behavioral effects of the acute consequences after coronavirus infection through a murine model. Material:Wild type C57 BL/6 mice were infected intranasally (i.n) with the murine coronavirus 3 (MHV-3). Methods:Mice were submitted to behavioral tests. Euthanasia was performed on the fth day after infection (5 dpi), and the brain tissue was subjected to plaque assays for viral titration, synaptosome, ELISA, histopathological and immunohistochemical analysis. Results:Increased viral titers associated with mild histological changes, including signs of neuronal degeneration, were observed in the cerebral cortex of infected mice. Importantly, MHV-3 infection induced an increase in cortical levels of glutamate and calcium, as well as increased levels of pro-in ammatory cytokines (IL-6, IFN-γ) and reduced levels of neuroprotective mediators (BDNF and CX3CL1) in the mice brain, which is suggestive of excitotoxicity. Finally, behavioral analysis showed impaired motor, anhedonic and anxietylike behaviors in animals infected with MHV-3. Conclusions:Overall, the data presented emulate many aspects of the acute neurological outcomes seen in patients with COVID-19. Therefore, this model may provide a preclinical platform to study acute neurological sequelae induced by coronavirus infection and test possible therapies.

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Negative Modulation of the Metabotropic Glutamate Receptor Type 5 as a Potential Therapeutic Strategy in Obesity and Binge-Like Eating Behavior

Cited by 19 publications

References 66 publications

Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington’s disease

Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington’s disease

Metabotropic Glutamate Receptor 5 Knockout Rescues Obesity Phenotype in a Mice Model of Huntington´s Disease

A suitable model to investigate acute neurological consequences of coronavirus infection

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