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

Abstract

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.