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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Veronesi, Vanessa Barbosa [1] ; Pioli, Mariana Rodrigues [1] ; de Souza, Dailson Nogueira [1] ; Teixeira, Caio Jordao [2] ; Murata, Gilson Masahiro [2, 3] ; Santos-Silva, Junia Carolina [1] ; Hecht, Fernanda Ballerini [1] ; Vicente, Julia Modesto [1] ; Bordin, Silvana [2] ; Anhe, Gabriel Forato [1]
Total Authors: 10
Affiliation:
[1] Univ Estadual Campinas, Fac Med Sci, Dept Pharmacol, 105 Alexander Flemming St, BR-13083881 Campinas, SP - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, 1524 Prof Lineu Prestes Ave, BR-05508000 Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Fac Med, Dept Med Clin, BR-01246403 Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: BIOMEDICINE & PHARMACOTHERAPY; v. 141, SEP 2021.
Web of Science Citations: 0
Abstract

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-HT2(c). 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. (AU)

FAPESP's process: 16/13138-9 - Effect of PPAR-gamma or PPAR-alpha agonists on the metabolic programing induced by maternal caloric restriction
Grantee:Vanessa Barbosa Veronesi
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
Grantee:Licio Augusto Velloso
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 15/23285-6 - Endocrine pancreas maturation and differentiation in offspring of females submitted to dexamethasone treatment during pregnancy
Grantee:Junia Carolina Rebelo dos Santos Silva
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 20/06397-3 - Study of cellular senescence in rodents subjected to Obesity
Grantee:Caio Jordão Teixeira
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 17/20742-2 - Effects of PPAR-gamma or PPAR-alpha agonists on the metabolic programming induced by maternal caloric restriction during pregnancy and lactation
Grantee:Gabriel Forato Anhê
Support type: Regular Research Grants
FAPESP's process: 19/03196-0 - Molecular mechanisms involved in the metabolic inflexibility of rats submitted to metabolic programming induced by prenatal excess of glucocorticoids
Grantee:Silvana Auxiliadora Bordin da Silva
Support type: Regular Research Grants