Circadian rhythms in gene expression: Relationship to physiology, disease, drug disposition and drug action☆

Abstract

Circadian rhythms (24 h cycles) are observed in virtually all aspects of mammalian function from expression of genes to complex physiological processes. The master clock is present in the suprachiasmatic nucleus (SCN) in the anterior part of the hypothalamus and controls peripheral clocks present in other parts of the body. Components of this core clock mechanism regulate the circadian rhythms in genome-wide mRNA expression, which in turn regulate various biological processes. Disruption of circadian rhythms can be either the cause or the effect of various disorders including metabolic syndrome, inflammatory diseases and cancer. Furthermore, circadian rhythms in gene expression regulate both the action and disposition of various drugs and affect therapeutic efficacy and toxicity based on dosing time. Understanding the regulation of circadian rhythms in gene expression plays an important role in both optimizing the dosing time for existing drugs and in development of new therapeutics targeting the molecular clock.

Mechanistic Modeling of the Effects of Glucocorticoids and Circadian Rhythms on Adipokine Expression

“…Circadian oscillations in gene expression and plasma biomarkers are important physiological factors that could contribute to quantitative variations and complexity for both pharmacokinetic and pharmacodynamic profiles for many endogenous compounds and drugs (Sukumaran et al, 2010a). All plasma markers and mRNA expression profiles except for adiponectin examined in our study displayed ro- bust circadian oscillations.…”

“…This suggests the importance of taking into account this variation in the baseline conditions that change as a function of time to quantitatively understand both the physiology and pharmacology of drug treatment. Circadian oscillations are important for efficient functioning of an organism and help the animal to anticipate, adapt, and respond to environmental changes (Sukumaran et al, 2010a). For example, as shown in Fig.…”

Circadian Signatures in Rat Liver: From Gene Expression to Pathways

“…Leptin, secreted from adipose tissue, plays an important role in appetite suppression in the brain. Plasma leptin levels are circadian with leptin peaking early in the nonactive phase, that is during the early dark phase in diurnal animals, such as monkeys and humans [66,67], and during the early to mid-light phase in nocturnal animals, such as rats and mice [68,69]. Neither feeding time nor adrenalectomy affects the rhythmicity of leptin release.…”

Circadian Rhythm, Health and Nutrition Relationship: Review

“…5 Yirmi dört saatte tamamlanan bu eşsiz zamanlama sistemi dünyanın rotasyonu ve gece-gündüz geçişlerinin yanı sıra; gel-git olayları, jeomanyetik etkiler, besin durumu ve sosyal etkileşimler tarafından da etkilenmektedir. 6 Sabit çevresel koşullar altında (hiçbir zaman ifadesinin olmadığı durumda), insanlarda ritmin yaklaşık 24,8 saatte bir kendini tekrarladığı göste-rilmiştir.…”