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

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.

mGluR5 ablation leads to age-related synaptic plasticity impairments and does not improve Huntington’s disease phenotype

“…Afterwards, F1 mice were crossed to obtain the lineages of interest (F2): WT, mGluR5 −/− , BACHD and BACHD/mGluR5 −/− (double mutant). Only F1 mice were used for crosses and the heterozygous F2 mice were discarded, as described previously 19 , 28 . This study was conducted using littermate male and female mice at the ages of 2, 6 and 12 months.…”

Methods of machine learning and big data analysis to establish the molecular mechanisms of the effects of racetams on the metabolism of adipose tissue

“…Аллостерическая регуляция mGluR1 и mGluR5 может использоваться для терапии расстройств, связанных с перееданием [58]. В частности, инактивация гена рецептора mGluR5 тормозит развитие ожирения у мышей [59].…”