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Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington's disease
Rebeca P M Santos1, Roberta Ribeiro1, Talita H Ferreira-Vieira2,3
1Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Ave. Antonio Carlos 6627, Belo Horizonte, MG, CEP 31270-901, Brazil.
Abstract:
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.
Insights
Genetic deletion of metabotropic glutamate receptor 5 (mGluR5) reduced obesity and inflammation in a mouse model of Huntington's disease (HD). This suggests mGluR5 plays a role in modulating adiposity and metabolic dysfunction.
Area of Science:
- Neuroscience
- Metabolic Research
- Immunology
Background:
- Obesity is a global health issue linked to metabolic dysfunction and chronic inflammation.
- These conditions increase the risk of comorbidities like atherosclerosis, diabetes, and insulin resistance.
- Huntington's disease (HD) mouse models can exhibit obesity, presenting an opportunity to study metabolic interventions.
Purpose of the Study:
- To investigate if genetic deletion of metabotropic glutamate receptor 5 (mGluR5) can alleviate metabolic and inflammatory issues in obese BACHD mice (an HD model).
- To determine the role of mGluR5 in adiposity and associated inflammatory markers in the context of HD.
Main Methods:
- Generated BACHD/mGluR5 knockout mice (double mutants) by crossing BACHD and mGluR5 knockout mice.
- Compared body weight, visceral adiposity, and adipose tissue inflammatory markers (adiponectin, leptin, IL-10/TNF ratio) between wild type, mGluR5 knockout, BACHD, and double mutant groups at different ages.
Main Results:
- Double mutant mice exhibited reduced body weight compared to BACHD mice across all tested ages.
- Visceral adiposity was decreased in double mutant mice at 6 months of age compared to BACHD mice.
- At 12 months, double mutant mice showed increased adiponectin, decreased leptin, and an elevated IL-10/TNF ratio in adipose tissue compared to BACHD mice, indicating reduced inflammation.
Conclusions:
- The absence of mGluR5 appears to reduce weight gain and visceral adiposity in BACHD mice.
- mGluR5 deletion may decrease the inflammatory state within visceral adipose tissue (VAT).
- These findings suggest a potential role for mGluR5 in the modulation of adiposity and related metabolic and inflammatory processes.
