The circadian clock in the brain’s suprachiasmatic nucleus coordinates circadian rhythms and the peripheral clocks, which are capable of independently monitoring normal physiology and metabolism as well as pathophysiology, and allow organismal adaptation to daily environmental cues. Environmental factors such as Western diet, sleep deprivation, and mental stress can influence the functioning of these organs due to circadian disruption. A ketogenic diet can profoundly and differentially affect liver and intestine clocks, resulting in metabolic dysfunctions [1]. The amplitude of clock-controlled genes and BMAL1 chromatin recruitment showed drastic alterations by this diet in the liver, but not in the intestine. Nuclear accumulations of PPARα in both gut and liver cells had different circadian phases. Gut and liver clocks responded in different ways to carbohydrate supplementation versus a ketogenic diet; hence these mechanisms are essential in the pathogenesis of cardio-metabolic diseases (CMDs), such as obesity, metabolic syndrome, diabetes mellitus, coronary artery disease, and hypertension. Disruption of physiological circadian rhythms has been associated with sleep and mood disorders, and there is growing evidence of the harmful consequences of shift work. © 2018 Nova Science Publishers, Inc.