2005). Bmal1 mutant mice also have disrupted circadian rhythmicity (Bunger et al. 2000), disrupted adipogenesis (Shimba et al. 2005), and demonstrate markers of metabolic syndrome (e.g., higher levels of triglycerides and glucose) (Marcheva et al. 2010; Rudic et al. 2004). Similarly, mutations in Cry genes disrupt hormonal rhythms (Fu et al. 2005; Yang et al. 2009) and Cry mutants show markers of metabolic syndrome (Okano et al. 2009). It should be noted that although some of these mutant mice demonstrate disrupted locomotion and feeding behaviors (i.e., wrong-time feeding), the abnormalities seem to be attributable to mutations in the circadian clock machinery rather than to appropriate feeding times because mice (e.g., Bmal1 mutant mice) that do exhibit normal activity/feeding patterns still exhibit markers of metabolic syndrome (Lamia et al. 2008; Marcheva et al. 2010). In addition to these effects of circadian rhythms on indices of metabolism, it is also important to consider the effect of circadian disruption on the immune system because chronic inflammation is a prominent feature associated with metabolic syndrome. Thus, the immune dysfunction that occurs upon circadian rhythm disruption may be a predisposing or exacerbating factor for metabolic syndrome. Epigenetic Alterations: Circadian Rhythm Disruption and Alcohol Epigenetics is the study of stable changes in gene expression that do not involve DNA sequence modifications but rather are the consequence of processes such as DNA methylation, histone modification (i.e., acetylation, methylation, phosphorylation, ubiquitinylation, ADP-ribosylation, and sumoylation), and noncoding micro-RNAs (miRNAs). These changes in gene expression are critical to optimize cellular function and for cellular development and differentiation. However, epigenetic changes also occur in response to environmental changes, including circadian rhythm disruption and alcohol use. Shift work (i.e., chronic circadian disruption) is associated with an increased incidence of cancer. Potential mechanisms for this relationship include changes in melatonin levels and levels of circadian clock genes (Straif et al. 2007). However, epigenetics also may influence circadian rhythm disruption and thereby affect cellular function. Indeed, long-term shift work affects promoter methylation of the circadian genes Clock and Cry2 (Zhu et al. 2011) with increased methylation of Clock (Hoffman et al. 2010a) and decreased methylation of Cry (Hoffman et al. 2010b) observed in cancer patients. Epigenetic changes also occur as a consequence of chronic circadian disruption in the promoter regions of genes encoding glucocorticoid receptors (important for hypothalamic�Cpituitary�C adrenal axis function), TNF��(a cytokine critical for cell functioning and inflammation), and IFN�� (Bollati et al. 2010).