Agomelatine reduces circulating triacylglycerides and hepatic steatosis in fructose-treated rats

Biomedicine & Pharmacotherapy

Mariana Rodrigues Pioli¹  Julia Modesto Vicente¹  Fernanda Ballerini Hecht¹  Gabriel Forato Anhê¹  Vanessa Barbosa Veronesi¹  Dailson Nogueira de Souza¹  Junia Carolina Santos-Silva¹  Gilson Masahiro Murata²  Caio Jordão Teixeira²  Silvana Bordin² 

[1] Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 105 Alexander Flemming St., Zip Code: 13083-881, Campinas, SP, Brazil;Department of Physiology and Biophysics, Institute of Biomedical Science, University of Sao Paulo, 1524 Prof. Lineu Prestes Ave., ICB 1, Zip Code: 05508-000, Sao Paulo, SP, Brazil;

关键词: Agomelatine;    Fructose;    Lipid metabolism;    Hepatic steatosis;    Melatonin;   

DOI  :  

来源: DOAJ

【 摘 要 】

Agomelatine (AGO) is an antidepressant drug with agonistic activity at melatonin receptor 1 (MT1) and MT2 and with neutral antagonistic activity at serotonin receptor 5-HT2C. Although experimental studies show that melatonin reduces hypertriglyceridemia and hepatic steatosis induced by excessive fructose intake, no studies have tested if AGO exerts similar actions. To address this issue we have treated male Wistar rats with fructose (15% in the drinking water) and/or AGO (40 mg/kg/day) for two weeks. AGO reduced body weight gain, feeding efficiency and hepatic lipid levels without affecting caloric intake in fructose-treated rats. AGO has also decreased very low-density lipoprotein (VLDL) production and circulating TAG levels after an oral load with olive oil. Accordingly, treatment with AGO reduced the hepatic expression of fatty acid synthase (Fasn), a limiting step for hepatic de novo lipogenesis (DNLG). The expression of apolipoprotein B (Apob) and microsomal triglyceride transfer protein (Mttp) in the ileum, two crucial proteins for intestinal lipoprotein production, were also downregulated by treatment with AGO. Altogether, the present data show that AGO mimics the metabolic benefits of melatonin when used in fructose-treated rats. This study also suggests that it is relevant to evaluate the potential of AGO to treat metabolic disorders in future clinical trials.

【 授权许可】

Unknown