Resetting Central and Peripheral Circadian Oscillators in Transgenic Rats

Yamazaki, Shin; Numano, Rika; Abe, Michikazu; Hida, Akiko; Takahashi, Ri Ichi; Ueda, Masatsugu; Block, Gene D.; Sakaki, Yoshiyuki; Menaker, Michael; Tei, Hajime

doi:10.1126/science.288.5466.682

Cited by 1,681 publications

(1,457 citation statements)

References 15 publications

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“…Light is the most potent timing cue or Zeitgeber of the circadian clock. However, whereas light directly resets the circadian clock in the SCN, changes in the lighting schedule are communicated to peripheral tissues via indirect output pathways emanating from the SCN (Yamazaki et al, 2000). This may explain why in comparison to the SCN oscillator peripheral clocks respond with a certain delay to changes in the lighting schedule.…”

Section: Synchronization Of the Liver Oscillator By Systemic Timing Cuesmentioning

confidence: 99%

The role of clock genes and rhythmicity in the liver

Schmutz

Albrecht

Ripperger

2012

Molecular and Cellular Endocrinology

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The liver is the important organ to maintain energy homeostasis of an organism. To achieve this, many biochemical reactions run in this organ in a rhythmic fashion. An elegant way to coordinate the temporal expression of genes for metabolic enzymes relies in the link to the circadian timing system. In this fashion not only a maximum of synchronization is achieved, but also anticipation of daily recurring events is possible. Here we will focus on the input and output pathways of the hepatic circadian oscillator and discuss the recently found flexibility of its circadian transcriptional networks.

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Section: Synchronization Of the Liver Oscillator By Systemic Timing Cuesmentioning

confidence: 99%

The role of clock genes and rhythmicity in the liver

Schmutz

Albrecht

Ripperger

2012

Molecular and Cellular Endocrinology

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“…Period1-luciferase (Per1-luc) Wistar rats [36] bred in our vivarium served as the experimental model in all experiments. A total of 64 rats were used to collect the data presented in this study: 28 4-to 8-month-old controls, and 26 rats aged to at least 24 months.…”

Section: Animals and Housingmentioning

confidence: 99%

Resetting of central and peripheral circadian oscillators in aged rats

Davidson

Yamazaki

Arble

et al. 2008

Neurobiology of Aging

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115

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The mammalian circadian timing system is affected by aging. Analysis of the suprachiasmatic nucleus (SCN) and of other circadian oscillators reveals age-related changes which are most profound in extra-SCN tissues. Some extra-SCN oscillators appear to stop oscillating in vivo or display altered phase relationships. To determine whether the dynamic behavior of circadian oscillators is also affected by aging we studied the resetting behavior of the Period1 transcriptional rhythm of peripheral and central oscillators in response to a 6 hr advance or delay in the light schedule. We employed a transgenic rat with a luciferase reporter to allow for real-time measurements of transcriptional rhythmicity. While phase-resetting in the SCN following an advance or a delay of the light cycle appears nearly normal in 2-year old rats, resynchronization of the liver was seriously disrupted. In addition, the arcuate nucleus and pineal gland exhibited faster resetting in aged rats relative to 4-8 month-old controls. The consequences of these deficits are unknown, but may contribute to organ and brain diseases in the aged as well as the health problems that are common in older shift-workers.

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“…However, the individuals eating the largest proportion of calories at night did not show an increased propensity to gain weight and were not heavier or fatter than monkeys eating the majority of their daily caloric intake during daytime hours (Sullivan et al 2005), suggesting that factors other than consumption of calories at night play a role in the predisposition of individuals with NES to obesity. Rodent studies show that feeding during the circadian phase when they normally sleep alters peripheral and central regulation of circadian rhythms (Damiola et al 2000;Yamazaki et al 2000). These animal models could be used to examine the metabolic and neuroendocrine consequences of consuming food during the night.…”

Section: Animal Models Of Nesmentioning

confidence: 99%

Relevance of animal models to human eating disorders and obesity

2008

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Background and rationale This review addresses the role animal models play in contributing to our knowledge about the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) and obesity. Objectives Explore the usefulness of animal models in complex biobehavioral familial conditions, such as AN, BN, and obesity, that involve interactions among genetic, physiologic, psychological, and cultural factors. Results and conclusionsThe most promising animal model to mimic AN is the activity-based anorexia rodent model leading to pathological weight loss. The paradigm incorporates reward elements of the drive for activity in the presence of an appetite and allows the use of genetically modified animals. For BN, the sham-feeding preparation in rodents equipped with a gastric fistula appears to be best suited to reproduce the postprandial emesis and the defects in satiety. Animal models that incorporate genes linked to behavior and mood may clarify biobehavioral processes underlying AN and BN. By contrast, a relative abundance of animal models has contributed to our understanding of human obesity. Both environmental and genetic determinants of obesity have been modeled in rodents. Here, we consider single gene mutant obesity models, along with models of obesigenic environmental conditions. The contributions of animal models to obesity research are illustrated by their utility for identifying genes linked to human obesity, for elucidating the pathways that regulate body weight and for the identification of potential therapeutic targets. The utility of these models may be further improved by exploring the impact of experimental manipulations on the behavioral determinants of energy balance.

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Resetting Central and Peripheral Circadian Oscillators in Transgenic Rats

Cited by 1,681 publications

References 15 publications

The role of clock genes and rhythmicity in the liver

The role of clock genes and rhythmicity in the liver

Resetting of central and peripheral circadian oscillators in aged rats

Relevance of animal models to human eating disorders and obesity

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