Abstract
Obesity is a multifactorial disease, which in turn contributes to the onset of comorbidities, such as diabetes and atherosclerosis. Moreover, there are only few options available for treating obesity, and most current pharmacotherapy causes severe adverse effects, while offering minimal weight loss. Literature shows that metabotropic glutamate receptor 5 (mGluR5) modulates central reward pathways. Herein, we evaluated the effect of VU0409106, a negative allosteric modulator (NAM) of mGluR5 in regulating feeding and obesity parameters. Diet-induced obese C57BL/6 mice were treated for 14 days with VU0409106, and food intake, body weight, inflammatory/hormonal levels, and behavioral tests were performed. Our data suggest reduction of feeding, body weight, and adipose tissue inflammation in mice treated with high-fat diet (HFD) after chronic treatment with VU0409106. Furthermore, a negative modulation of mGluR5 also reduces binge-like eating, the most common type of eating disorder. Altogether, our results pointed out mGluR5 as a potential target for treating obesity, as well as related disorders.
Highlights
Obesity prevalence is expanding in most countries according to the World Health Organization (Blüher, 2019)
We observed a reduction of inflammatory cytokine levels IL-12p70, Tumor necrosis factor (TNF)-α, and interferon γ (IFN-γ) in high-fat diet (HFD) mice treated with VU0409106 7.5 mg/kg in the adipose tissue of C57BL/6 obese mice (one-way analysis of variance (ANOVA), IL-12p70 F(3,23) = 3.116, p = 0.0459; TNF-α F(3,24) = 3.904, p = 0.021; and IFN-γ F(3,27) = 3.962, p = 0.0184) (Figures 3A–C)
Results showed an increase in hypothalamic adiponectin levels in mice fed with HFD, no other difference regarding serum insulin, adiponectin, triglycerides, and inflammatory markers outside epididymal adipose tissue was observed between HFD and control group (Table 1)
Summary
Obesity prevalence is expanding in most countries according to the World Health Organization (Blüher, 2019). Worldwide obesity numbers nearly tripled since 1975 (Blüher, 2019). Obesity is defined as an abnormal accumulation of body fat, associated with genetics, hormones, and environmental factors (GonzálezMuniesa et al, 2017). Obesity increases the risk of several chronic conditions, including cardiovascular diseases, diabetes, cancer, psychiatric disorders, and many others (Kopelman, 2007). Changes leading to a series of physiological imbalances can be established in obese individuals, such as dyslipidemia and chronic inflammatory response (Dandona et al, 2004; Van Gaal et al, 2006). The progressive adipose tissue expansion in obesity is associated with insufficient angiogenesis, leading to hypoxia, cellular stress, oxidative damage, and necrosis, triggering an inflammatory
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