Impaired daily glucocorticoid rhythm in Per1 Brd mice
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Biological clocks have evolved in all kinds of organisms in order to anticipate and adjust to the daily light–dark cycle. Within the last decade, the molecular machinery underlying the circadian system was unraveled. In the present study, the impact of the loss of the Per1 or Per2 genes, key components of the core clock oscillator, on body mass, food and water intake, glucose metabolism, and hypothalamic-pituitary-adrenal axis, was investigated in the Per1 Brd and Per2 Brd mouse models. The results reveal that the lack of Per1 but not Per2 has severe consequences for the regulation of these parameters. Specifically, in Per1 Brd animals, we found an impaired daily glucocorticoid rhythm, with markedly elevated levels during the day compared to control animals. In addition, Per1 Brd mice showed significant differences in body mass as well as food and water intake. Although the Per1 Brd are lighter than wildtype mice, food and water intake per gram body mass is elevated. In addition, the Per1 Brd mice exhibit an increased glucose metabolism after i.p. injection with glucose. In conclusion, our study presents first evidence for a link between an altered metabolism in Per1 and Per2 deficient mice, which in the case of the Per1 Brd animals might be due to an impaired corticosterone rhythm.
KeywordsAdrenocortical activity Circadian rhythm Clock gene Fecal glucocorticoid metabolites Period
- HPA axis
Area under curve
This work has been supported by the German Research Foundation GRK 705 (RD). Prof. Heldmaier kindly provided the metabolic cages. We thank H. Oster and two anonymous reviewers for critical comments on previous versions of the manuscript. All procedures described regarding animal experimentation were in accordance with the animal protection act of the Federal Republic of Germany and the guidelines of the European Union (86/609/EEC). The experiments were approved by the district government of Hannover, Germany.
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