Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Ave. Antonio Carlos 6627, Belo Horizonte, MG, CEP 31270-901, Brazil.
Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, CEP 31270-901, Brazil.
Sci Rep. 2022 Apr 4;12(1):5621. doi: 10.1038/s41598-022-08924-4.
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.
肥胖代表着一个全球性的健康问题，其特征是代谢功能紊乱和低度慢性炎症状态，这会增加合并症的风险，如动脉粥样硬化、糖尿病和胰岛素抵抗。在这里，我们检验了这样一个假设，即代谢型谷氨酸受体 5 (mGluR5) 的基因缺失可能会改善 BACHD 小鼠（一种具有肥胖表型的亨廷顿病的小鼠模型）存在的代谢和炎症特征。为此，我们将 BACHD 小鼠与 mGluR5 基因敲除（mGluR5）小鼠进行杂交，以获得以下组别：野生型（WT）、mGluR5、BACHD 和 BACHD/mGluR5（双突变小鼠）。我们的结果表明，与 BACHD 小鼠相比，在所有测试的年龄段，双突变小鼠的体重都有所下降，而在 6 个月大时，内脏脂肪也有所减少。此外，与 BACHD 小鼠相比，12 个月大的双突变小鼠的脂肪组织中脂联素水平增加，瘦素水平降低，IL-10/TNF 比值升高。综上所述，我们的初步数据表明，mGluR5 的缺失可减少 BACHD 小鼠的体重增加和内脏脂肪堆积，并降低内脏脂肪组织（VAT）的炎症状态，这表明 mGluR5 可能在肥胖调节中发挥作用。
