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      Pineal melatonin is a circadian time-giver for leptin rhythm in Syrian hamsters

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          Abstract

          Nocturnal secretion of melatonin from the pineal gland may affect central and peripheral timing, in addition to its well-known involvement in the control of seasonal physiology. The Syrian hamster is a photoperiodic species, which displays gonadal atrophy and increased adiposity when adapted to short (winter-like) photoperiods. Here we investigated whether pineal melatonin secreted at night can impact daily rhythmicity of metabolic hormones and glucose in that seasonal species. For that purpose, daily variations of plasma leptin, cortisol, insulin and glucose were analyzed in pinealectomized hamsters, as compared to sham-operated controls kept under very long (16 h light/08 h dark) or short photoperiods (08 h light/16 h dark). Daily rhythms of leptin under both long and short photoperiods were blunted by pinealectomy. Furthermore, the phase of cortisol rhythm under a short photoperiod was advanced by 5.6 h after pinealectomy. Neither plasma insulin, nor blood glucose displays robust daily rhythmicity, even in sham-operated hamsters. Pinealectomy, however, totally reversed the decreased levels of insulin under short days and the photoperiodic variations in mean levels of blood glucose (i.e., reduction and increase in long and short days, respectively). Together, these findings in Syrian hamsters show that circulating melatonin at night drives the daily rhythmicity of plasma leptin, participates in the phase control of cortisol rhythm and modulates glucose homeostasis according to photoperiod-dependent metabolic state.

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          Most cited references40

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          Resetting of circadian time in peripheral tissues by glucocorticoid signaling.

          In mammals, circadian oscillators reside not only in the suprachiasmatic nucleus of the brain, which harbors the central pacemaker, but also in most peripheral tissues. Here, we show that the glucocorticoid hormone analog dexamethasone induces circadian gene expression in cultured rat-1 fibroblasts and transiently changes the phase of circadian gene expression in liver, kidney, and heart. However, dexamethasone does not affect cyclic gene expression in neurons of the suprachiasmatic nucleus. This enabled us to establish an apparent phase-shift response curve specifically for peripheral clocks in intact animals. In contrast to the central clock, circadian oscillators in peripheral tissues appear to remain responsive to phase resetting throughout the day.
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            Leptin.

            The discovery of the adipose-derived hormone leptin has generated enormous interest in the interaction between peripheral signals and brain targets involved in the regulation of feeding and energy balance. Plasma leptin levels correlate with fat stores and respond to changes in energy balance. It was initially proposed that leptin serves a primary role as an anti-obesity hormone, but this role is commonly thwarted by leptin resistance. Leptin also serves as a mediator of the adaptation to fasting, and this role may be the primary function for which the molecule evolved. There is increasing evidence that leptin has systemic effects apart from those related to energy homeostasis, including regulation of neuroendocrine and immune function and a role in development.
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              Melatonin reduces body weight gain in Sprague Dawley rats with diet-induced obesity.

              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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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                27 May 2015
                2015
                : 9
                : 190
                Affiliations
                [1] 1Laboratory of Biology and Health, Faculty of Science, Abdelmalek Essaâdi University Tetouan, Morocco
                [2] 2Regulation of Circadian Clocks Team, Institute for Cellular and Integrative Neurosciences, UPR3212, Centre National de la Recherche Scientifique and University of Strasbourg Strasbourg, France
                Author notes

                Edited by: Hubert Vaudry, University of Rouen, France

                Reviewed by: Andries Kalsbeek, University of Amsterdam, Netherlands; Jonathan Johnston, University of Surrey, UK

                *Correspondence: Etienne Challet and Patrick Vuillez, Institute for Cellular and Integrative Neurosciences, UPR3212, Centre National de la Recherche Scientifique and University of Strasbourg, 5 rue Blaise Pascal, 67000 Strasbourg, France challet@ 123456inci-cnrs.unistra.fr ; vuillez@ 123456inci-cnrs.unistra.fr

                This article was submitted to Neuroendocrine Science, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2015.00190
                4444759
                26074760
                508f351a-8e83-4ab1-aeff-f9027c75b091
                Copyright © 2015 Chakir, Dumont, Pévet, Ouarour, Challet and Vuillez.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 December 2014
                : 11 May 2015
                Page count
                Figures: 5, Tables: 2, Equations: 0, References: 45, Pages: 9, Words: 6714
                Categories
                Endocrinology
                Original Research

                Neurosciences
                golden hamster,pinealectomy,photoperiod,cortisol rhythm,plasma glucose
                Neurosciences
                golden hamster, pinealectomy, photoperiod, cortisol rhythm, plasma glucose

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