HDAC3 inhibition protects against peripheral and central alterations in an animal model of obesity

Background: Obesity is a multifactorial disease with epigenetic manifestations that increases the prevalence of associated comorbidities such as metabolic syndrome, cardiovascular dysfunction, and major depression disorder. Given the aforementioned, a search for new pharmacological alternatives for the treatment of this disease is necessary. The current study aimed to evaluate the effects of histone deacetylase-3 (HDAC3) inhibition caused by RGFP966 (a benzamide-type HDAC inhibitor selective for HDAC3) administration, in an animal model of obesity induced by high-fat diet (HFD).

Methods: Adult male mice C57BJ/6 were fed with a normal pellet diet (NPD) or HFD for 120 days. The HDAC3 inhibitor (RGFP966; 10 mg/kg; sc) was administered on the 91st to 120th day of the experiment (per 30 days). After the last inhibitor administration, animals were euthanized, blood was collected, and the hippocampus was removed for biochemical determinations.

Results: In an overall manner, the administration of RGFP966 protected against changes in body weight gain, glucose, insulin, lipid profile, adipokines, and increase of hippocampal proinflammatory cytokines levels caused by HFD.

Conclusion: Therefore, HDAC3 inhibition can represent a promising pharmacological target for the treatment of obesity.