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Melatonin Reduces Body Weight Gain in Sprague Dawley Rats with Diet-Induced Obesity

Unité Mixte de Recherche 5018, Centre National de la Recherche Scientifique, Université Paul Sabatier, Institut Fédératif de Recherche 31 (B.P.-M., M.D., A.B., K.L., L.C., L.P.), Centre Hospitalier Universitaire Rangueil, 31059 Toulouse Cedex 9, France; and Institut de Recherche International Servier (P.D., P.R.), Courbevoie 92415, France

Address all correspondence and requests for reprints to: Dr. Luc Pénicaud, Unité Mixte de Recherche 5018-Centre National de la Recherche Scientifique, Centre Hospitalier Universitaire Rangueil, bâtiment L1, 1 avenue J. Poulhès, 31059 Toulouse Cedex 9, France. E-mail: penicaud{at}toulouse.inserm.fr.

Melatonin is involved in the regulation of seasonal obesity in various species, including some rodents. This involvement has been demonstrated in nonphotoperiodic rodents like rats, but only in models of enhanced body weight such as genetically obese or middle-aged rats. The aim of this investigation was to determine the effects of melatonin on body weight and metabolic parameters in a model closer to that observed in Western populations, i.e. Sprague Dawley rats fed a high-fat diet. They were treated for 3 wk with melatonin (30 mg/kg) 4 h after lights-on [Zeitgeber time (ZT) 4] or 1 h before lights-out (ZT11). Given at ZT11, melatonin decreased body weight gain and feed efficiency by half. Melatonin had no effect on plasma insulin level, but it decreased plasma glucose (13%), leptin (28%), and triglyceride (28%) levels. Furthermore, in pinealectomized high-fat diet rats, body weight gain and feed efficiency were increased 4 wk after surgery. Adipose tissue weight, insulinemia, and glycemia had a tendency to increase. Treatment with melatonin prevented in part these changes. These data demonstrate that melatonin may act as a regulator of body weight in a model of obesity and may prevent some of the side effects on glucose homeostasis such as decreased insulin sensitivity.

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