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

Autor: Machado FR; Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa, Campus Itaqui, Itaqui, RS, 97650-000, Brazil., Boeira SP; Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa, Campus Itaqui, Itaqui, RS, 97650-000, Brazil., Bortolotto VC; Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa, Campus Itaqui, Itaqui, RS, 97650-000, Brazil., Araujo SM; Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa, Campus Itaqui, Itaqui, RS, 97650-000, Brazil., Poetini MR; Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa, Campus Itaqui, Itaqui, RS, 97650-000, Brazil., Viana CE; Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa, Campus Itaqui, Itaqui, RS, 97650-000, Brazil., Prigol M; Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa, Campus Itaqui, Itaqui, RS, 97650-000, Brazil., Souza LC; Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa, Campus Itaqui, Itaqui, RS, 97650-000, Brazil., de Gomes MG; Laboratory of Pharmacological and Toxicological Evaluations Applied to Bioactive Molecules, LaftamBio Pampa, Federal University of Pampa, Campus Itaqui, Itaqui, RS, 97650-000, Brazil. marcelogomesdegomes@hotmail.com.
Jazyk: angličtina
Zdroj: Pharmacological reports : PR [Pharmacol Rep] 2023 Oct; Vol. 75 (5), pp. 1177-1186. Date of Electronic Publication: 2023 Sep 12.
DOI: 10.1007/s43440-023-00528-7
Abstrakt: 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.
(© 2023. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)
Databáze: MEDLINE
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