Insulin-FOXO3 Signaling Modulates Circadian Rhythms via Regulation of Clock Transcription

Chaves, Inês; Horst, Gijsbertus T. J. van der; Schellevis, Raymond D.; Nijman, Romana; Koerkamp, Marian J. A. Groot; Holstege, Frank C.P.; Smidt, Marten P.; Hoekman, Marco F.M.

doi:10.1016/j.cub.2014.04.018

Cited by 77 publications

(69 citation statements)

References 34 publications

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“…Although the detailed etiologies still need to be unraveled, it is evident that there is a strong relationship between major depression and circadian disruption (Karatsoreos, 2014). Interestingly, clock is a transcriptional target of FoxO3a and the insulin-FoxO3a-Clock signaling pathway plays a key role in the modulation of circadian rhythms, for instance, knock down of FoxO3a dampens circadian amplitude (Chaves et al, 2014;Zheng et al, 2007). These studies revealed an important new role for FoxOs in the regulation of depressive behavior.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Forkhead box O transcription factors as possible mediators in the development of major depression

et al. 2015

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Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Forkhead box O transcription factors as possible mediators in the development of major depression

et al. 2015

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“…The pGL3-EV showed a 6.5-fold increase in luminescence (FoxO6-GFP/GFP) (Fig. 6D), suggesting that FoxO6 may regulate transcription in general, as has previously been suggested (22). Importantly, promoter elements containing the confirmed in vivo FoxO6-binding element (pGL3-DBE4) show a significant increase in RLUs (P < 0.01) (FoxO6-GFP/GFP) compared with the control (pGL3-EV) …”

Section: Foxo6 Interacts With Specific Daf-16-binding Elements Withinmentioning

confidence: 63%

FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development

Paap

Oosterbroek

Wagemans

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in FoxO6 +/− and FoxO6 −/− mice, showing migrating neurons halted in the intermediate zone. Using a FoxO6-directed siRNA approach, we substantiate the requirement of FoxO6 for a correct radial migration in the developing neocortex. Subsequent genome-wide transcriptome analysis reveals altered expression of genes involved in cell adhesion, axon guidance, and gliogenesis upon silencing of FoxO6. We then show that FoxO6 binds to DAF-16-binding elements in the Plexin A4 (Plxna4) promoter region and affects Plxna4 expression. Finally, ectopic Plxna4 expression restores radial migration in FoxO6 +/− and siRNA-mediated knockdown models. In conclusion, the presented data provide insights into the molecular mechanisms whereby transcriptional programs drive cortical development.

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“…Meal-induced insulin secretion leads to acute changes of clock gene expression in the liver, including upregulation of Per2 mRNA and downregulation of Rev-erb mRNA [62]. Among the activated intracellular pathways, FoxO3 signalling is able to activate the transcription of the circadian gene Clock [63]. Insulin-mediated signals, however, are probably not the only ones that allow the liver to be synchronized to feeding cues because streptozocin treatment that severely damages -cells does not prevent hepatic synchronization to feeding [7].…”

Section: Insulin As a Postfeeding Timermentioning

confidence: 99%

Keeping circadian time with hormones

Challet

2015

Diabetes Obesity Metabolism

122

106

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Daily variations of metabolism, physiology and behaviour are controlled by a network of coupled circadian clocks, comprising a master clock in the suprachiasmatic nuclei of the hypothalamus and a multitude of secondary clocks in the brain and peripheral organs. Light cues synchronize the master clock that conveys temporal cues to other body clocks via neuronal and hormonal signals. Feeding at unusual times can reset the phase of most peripheral clocks. While the neuroendocrine aspect of circadian regulation has been underappreciated, this review aims at showing that the role of hormonal rhythms as internal time-givers is the rule rather than the exception. Adrenal glucocorticoids, pineal melatonin and adipocyte-derived leptin participate in internal synchronization (coupling) within the multi-oscillatory network. Furthermore, pancreatic insulin is involved in food synchronization of peripheral clocks, while stomach ghrelin provides temporal signals modulating behavioural anticipation of mealtime. Circadian desynchronization induced by shift work or chronic jet lag has harmful effects on metabolic regulation, thus favouring diabetes and obesity. Circadian deregulation of hormonal rhythms may participate in internal desynchronization and associated increase in metabolic risks. Conversely, adequate timing of endocrine therapies can promote phase-adjustment of the master clock (e.g. via melatonin agonists) and peripheral clocks (e.g. via glucocorticoid agonists). Keywords: circadian rhythm, desynchronization, diabetes, feeding time, ghrelin, glucocorticoid, insulin, leptin, melatonin, metabolic disturbances, obesity Date submitted 23 April 2015; date of final acceptance 3 June 2015 IntroductionThe circadian system allows metabolic, physiological and behavioural functions to oscillate (i.e. to alternate periods of activity and rest over 24 h), and by organizing a temporal segregation, it avoids the simultaneous occurrence of conflicting behaviours (e.g. feeding and sleeping) or conflicting cellular functions (e.g. glycogenesis and glycolysis), to name a few. The circadian system also allows these functions to anticipate or be in phase with daily predictable events in the environment, such as the daily alternation of light and dark.The circadian system consists of a network of endogenous clocks, coupled by internal signals via the autonomic nervous system and hormonal rhythms, and synchronized by external cues, including light and food. Ambient light detected by the retina, which itself contains a circadian clock, is the most powerful synchronizer of the master clock located in the suprachiasmatic nuclei of the hypothalamus. By contrast, food ingestion modulates the phase of the peripheral clocks, but usually not the oscillations of the suprachiasmatic clock that remain synchronized to light. This review aims at describing the reciprocal links between the circadian system and hormones involved in metabolism. As will be detailed, circadian clocks control the daily rhythms of circulating hormones. In turn, hormonal cues...

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Insulin-FOXO3 Signaling Modulates Circadian Rhythms via Regulation of Clock Transcription

Cited by 77 publications

References 34 publications

Forkhead box O transcription factors as possible mediators in the development of major depression

Forkhead box O transcription factors as possible mediators in the development of major depression

FoxO6 affects Plxna4-mediated neuronal migration during mouse cortical development

Keeping circadian time with hormones

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