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Negative Modulation of the Metabotropic Glutamate Receptor Type 5 as a Potential Therapeutic Strategy in Obesity and

Tadeu P D Oliveira1, Bruno D C Gonçalves1, Bruna S Oliveira2

  • 1Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Frontiers in Neuroscience
|March 1, 2021
PubMed

Insights

Metabotropic glutamate receptor 5 (mGluR5) modulation with VU0409106 reduced feeding and body weight in obese mice. This finding suggests mGluR5 as a potential therapeutic target for obesity and eating disorders.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Metabolic Disease Research

Background:

  • Obesity is a complex disease with limited effective treatments and significant adverse effects from current pharmacotherapies.
  • Metabotropic glutamate receptor 5 (mGluR5) plays a role in modulating central reward pathways, suggesting its potential involvement in feeding behaviors.
  • Existing obesity treatments offer minimal weight loss and often cause severe side effects.

Purpose of the Study:

  • To evaluate the efficacy of VU0409106, a negative allosteric modulator (NAM) of mGluR5, in regulating feeding and obesity parameters.
  • To investigate the impact of mGluR5 modulation on body weight, food intake, and related physiological markers in diet-induced obese mice.

Main Methods:

  • Diet-induced obese C57BL/6 mice were chronically treated with VU0409106 for 14 days.
  • Measurements included food intake, body weight, adipose tissue inflammation, hormonal levels, and behavioral tests assessing eating patterns.

Main Results:

  • Chronic treatment with VU0409106 led to a reduction in feeding and body weight in obese mice.
  • VU0409106 treatment decreased adipose tissue inflammation.
  • Negative modulation of mGluR5 was also found to reduce binge-like eating behaviors.

Conclusions:

  • Metabotropic glutamate receptor 5 (mGluR5) is identified as a potential therapeutic target for managing obesity.
  • Targeting mGluR5 may offer a novel strategy for treating obesity and associated eating disorders like binge eating.
Keywords:
glutamatehigh-fatinflammationmGluR5obesity

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