Academic journal article Alcohol Research: Current Reviews

Circadian Disruption: Potential Implications in Inflammatory and Metabolic Diseases Associated with Alcohol

Academic journal article Alcohol Research: Current Reviews

Circadian Disruption: Potential Implications in Inflammatory and Metabolic Diseases Associated with Alcohol

Article excerpt

Circadian Disruption and Society

The circadian clock is a sophisticated mechanism that functions to synchronize (i.e., entrain) endogenous systems with the 24-hour day in a wide variety of organisms, from simple organisms such as fungi up to the complex mammalian systems. Circadian rhythms control a variety of biological processes, including sleep/wake cycles, body temperature, hormone secretion, intestinal function, metabolic glucose homeostasis, and immune function. Functional consequences of modern-day society, such as late-night activity, work schedules that include long-term night shifts and those in which employees change or rotate shifts (i.e., shift work), and jet lag are substantial environmental disruptors of normal circadian rhythms. Fifteen percent of American workers perform shift work (Bureau of Labor Statistics 2005), indicating the pervasiveness of circadian disruption as a normal part of modern-day society. This change from the diurnal lifestyle of our ancestors to one that is more prominently nocturnal results in misalignment between natural rhythms based on the 24-hour day and behavioral activity patterns (i.e, circadian misalignment). Circadian misalignment has a significant detrimental effect on cell, tissue, and whole-organism function. These alterations can manifest in humans as chronic health conditions, such as metabolic syndrome, (1) diabetes, cardiovascular disease, cancer, and intestinal disorders (Karlsson et al. 2001; Morikawa et al. 2005; Schernhammer et al. 2003; Penev et al. 1998; Caruso et al. 2004). The increased prevalence of diseases associated with circadian disruption underscores the need to better understand how circadian disruption can wreak havoc in so many different ways throughout the body.

Central and Peripheral Circadian Rhythms

The master or central circadian clock (i.e., "pacemaker") is located in the suprachiasmatic nucleus (SCN) in the anterior hypothalamus in the brain (Turek 1981) (see figure 1). The SCN is regulated by light stimulating retinal ganglion cells in the eye (Berson et al. 2002), and it is by this mechanism that light directs central circadian rhythms. Circadian rhythms are found in nearly every cell in the body, including the periphery, encompassing the immune system, heart, adipose tissue, pancreas, and liver (Allaman-Pillet et al. 2004; Boivin et al. 2003; Storch et al. 2002; Yoo et al. 2004; Zvonic et al. 2006). The SCN synchronizes circadian rhythms found in the periphery (figure 2A) via several mechanisms, including communication with nerve cells that influence visceral functions such as digestion, heart rate, etc., via direct release of the hormones oxytocin and vasopression into the general vasculature or indirectly via release of local signals that affect the release of hormones from the anterior pituitary gland (i.e., neuroendocrine and autonomic neurons) (Buijs et al. 2003). In addition, peripheral circadian rhythms can be regulated by external factors other than central light-entrained rhythms. For instance, abnormal feeding patterns can cause peripheral circadian rhythms (i.e., in the intestine and liver) to become misaligned with central rhythms if feeding is out of synch with the normal 24-hour pattern, a phenomenon that can be observed in both animals and humans (see figure 2B). Peripheral tissues express self-sustained rhythms that are able to function independent of the central clock in the SCN. For example, following SCN lesion that terminates central circadian rhythmicity, peripheral circadian clocks continue to demonstrate rhythmicity; however, peripheral rhythms become desynchronized from each other over time (Yoo et al. 2004) (see figure 2C). This internal misalignment is particularly detrimental because peripheral circadian clocks directly regulate up to 5 to 20 percent of the genome (i.e., so-called clock-controlled genes) (Bozek et al. 2009). Furthermore, reports indicate that 3 to 20 percent of the entire genome demonstrates 24-hour oscillations in gene expression, including genes critical for metabolic processes. …

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