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part by the rhythmic expression of clock genes in the suprachiasmatic nucleus (SCN) ( Nader et al . 2010 ). These clock genes ( Bmal1/Arntl , Clock , Per1 , Per2 , Cry1 and Cry2 ) form a molecular network of transcriptional–translational loops to
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( Welsh et al. 1995, 2004 , Balsalobre et al. 1998 , Lowrey & Takahashi 2004 , Nagoshi et al. 2004 , Yoo et al. 2004 ). For instance, it has been reported that external temperature cycles can evoke rhythmic clock gene expression in Rat-1
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cells, the molecular machinery is composed of the same clock genes and their protein products connected by autoregulatory feedback loops. The major loop comprises the PAS domain helix-loop-helix transcriptional activators BMAL1 and CLOCK forming
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located in numerous (if not all) tissues ( Fig. 1 ). The molecular functioning of this set of oscillators is similar in peripheral and central clocks and is based on translational–transcriptional feedback loops of a set of genes called clock genes, whose
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Melatonin-based photoperiod time-measurement and circannual rhythm generation are long-term time-keeping systems used to regulate seasonal cycles in physiology and behaviour in a wide range of mammals including man. We summarise recent evidence that temporal, melatonin-controlled expression of clock genes in specific calendar cells may provide a molecular mechanism for long-term timing. The agranular secretory cells of the pars tuberalis (PT) of the pituitary gland provide a model cell-type because they express a high density of melatonin (mt1) receptors and are implicated in photoperiod/circannual regulation of prolactin secretion and the associated seasonal biological responses. Studies of seasonal breeding hamsters and sheep indicate that circadian clock gene expression in the PT is modulated by photoperiod via the melatonin signal. In the Syrian and Siberian hamster PT, the high amplitude Per1 rhythm associated with dawn is suppressed under short photoperiods, an effect that is mimicked by melatonin treatment. More extensive studies in sheep show that many clock genes (e.g. Bmal1, Clock, Per1, Per2, Cry1 and Cry2) are expressed in the PT, and their expression oscillates through the 24-h light/darkness cycle in a temporal sequence distinct from that in the hypothalamic suprachiasmatic nucleus (central circadian pacemaker). Activation of Per1 occurs in the early light phase (dawn), while activation of Cry1 occurs in the dark phase (dusk), thus photoperiod-induced changes in the relative phase of Per and Cry gene expression acting through PER/CRY protein/protein interaction provide a potential mechanism for decoding the melatonin signal and generating a long-term photoperiodic response. The current challenge is to identify other calendar cells in the central nervous system regulating long-term cycles in reproduction, body weight and other seasonal characteristics and to establish whether clock genes provide a conserved molecular mechanism for long-term timekeeping.
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. 2004 , Laermans et al . 2015 ). Diurnal rhythms in plasma ghrelin levels and gastric ghrelin expression are abolished in mice that lack the core clock gene Bmal1 , indicating that ghrelin levels are regulated by the circadian clock ( Laermans et al
Third Faculty of Medicine, Charles University, Prague, Czech Republic
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clock genes (e.g. Per1,2 , Cry1,2 , Bmal1 , Nr1d1 ) and temporally controls expression of tissue-specific physiologically relevant genes. The clock in the CP is self-autonomous because it can run in absence of any rhythmic input, as demonstrated in
Center of Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Germany
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Institute for Human Genetics, Epigenetics and Metabolism Lab, University of Lübeck, Lübeck, Germany
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Center of Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Germany
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Center of Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Germany
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Institute for Human Genetics, Epigenetics and Metabolism Lab, University of Lübeck, Lübeck, Germany
German Center for Diabetes Research (DZD), Helmholtz Zentrum München, Bayern, Germany
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Center of Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Germany
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from Clock gene mutant mice suggest that the general metabolic benefits of VSG persist despite a dysfunctional circadian system ( Arble et al. 2015 ). The interplay between surgery and circadian organization may influence metabolic and behavioral
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, the SCN exerts tight circadian control over many biological processes through endogenous rhythms generated by positive and negative feedback gene transcription and translation loops of clock genes, including Clock , Bmal1 , Per1-3 , Cry 1-2 , and
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Tokyo Adachi Hospital, Adachi, Tokyo, Japan
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, Shimba et al. 2011 ). Conversely, obesity simultaneously decreases the expression of clock genes in each tissue; for example, a high-fat diet can alter the rhythmic expression of clock genes in the liver and the adipose tissue and affect behavioral
