title: Short-term melatonin consumption protects the heart of obese rats independent of body weight change and visceral adiposity.
abstract: Chronic melatonin treatment has been shown to prevent the harmful effects of diet-induced obesity and reduce myocardial susceptibility to ischaemia-reperfusion injury (IRI). However, the exact mechanism whereby it exerts its beneficial actions on the heart in obesity/insulin resistance remains unknown. Herein, we investigated the effects of relatively short-term melatonin treatment on the heart in a rat model of diet-induced obesity. Control and diet-induced obese Wistar rats (fed a high calorie diet for 20 wk) were each subdivided into three groups receiving drinking water with or without melatonin (4 mg/kg/day) for the last 6 or 3 wk of experimentation. A number of isolated hearts were perfused in the working mode, subjected to regional or global ischaemia-reperfusion; others were nonperfused. Metabolic parameters, myocardial infarct sizes (IFS), baseline and postischaemic activation of PKB/Akt, ERK42/44, GSK-3β and STAT-3 were determined. Diet-induced obesity caused increases in body weight gain, visceral adiposity, fasting blood glucose, serum insulin and triglyceride (TG) levels with a concomitant cardiac hypertrophy, large postischaemic myocardial IFSs and a reduced cardiac output. Melatonin treatment (3 and 6 wk) decreased serum insulin levels and the HOMA index (P < 0.05) with no effect on weight gain (after 3 wk), visceral adiposity, serum TG and glucose levels. It increased serum adiponectin levels, reduced myocardial IFSs in both groups and activated baseline myocardial STAT-3 and PKB/Akt, ERK42/44 and GSK-3β during reperfusion. Overall, short-term melatonin administration to obese/insulin resistant rats reduced insulin resistance and protected the heart against ex vivo myocardial IRI independently of body weight change and visceral adiposity.
authors.affiliation: Division of Medical Physiology, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Frederic
authors.initials: F
authors.lastname: Nduhirabandi
authors.forename: Barbara
authors.initials: B
authors.lastname: Huisamen
authors.forename: Hans
authors.initials: H
authors.lastname: Strijdom
authors.forename: Dee
authors.initials: D
authors.lastname: Blackhurst
authors.forename: Amanda
authors.initials: A
authors.lastname: Lochner
mesh_terms: D000818:Animals; D001835:Body Weight; D006321:Heart / Q000187:drug effects*; D050152:Intra-Abdominal Fat; D008550:Melatonin / Q000008:administration & dosage*; D009765:Obesity / Q000503:physiopathology*; D051381:Rats
chemical_list: D008550:Melatonin
keywords: cardioprotection; insulin resistance; intracellular signalling; melatonin; myocardial ischaemia-reperfusion injury; obesity