In mammals, the approximate 24-h rhythm in behavior and physiology is generally existed, such as wake/ sleep cycle, blood pressure, body temperature and concentration of melatonin. The circadian rhythms result from the cell-autonomous and self-sustained oscillators (circadian clocks), which rely on interlocking transcription/translational feedback loops involving a series of clock genes (Clock, Bmal1, Per, Cry, Dec etc.) and their proteins (1). The mammalian circadian clocks are composed of a master clock located in the hypothalamic suprachiasmatic nucleus (SCN), and of many peripheral clocks in tissues and extra-SCN brain regions (2). The master clock is mainly entrained by the light cue, while the peripheral clocks are not only affected by the SCN clock but also entrained by the food cue (3). Moreover, feeding could take over part of the SCN signaling, and affect internal synchrony between the master clock and the peripheral clocks. Nutrient Components and Circadian RhythmsNutrient components have been identified as important factors to entrain the peripheral circadian clocks (4).Glucose is a particularly potent entraining factor for peripheral clocks (5). Min-Dian Li et al. found that high concentration of glucose increased the transcription levels of Bmal1 and Cry1 genes without the alteration of the phase of Bmal1 cycling, and low concentration of glucose delayed the phase of BMAL1 protein accumulation via western blot (6). How could glucose influence the circadian clock and further affect the following metabolic process aroused extensive attention. Some researchers revealed that cellular nutrient sensors such as nuclear receptors were proposed as candidates for the circadian clock entrainment by nutrient components (7,8). A recent study showed that the O-GlcNAc signaling entrained the circadian clock by inhibiting BMAL1/ CLOCK ubiquitination, which may be the molecular mechanism underlying the glucose entrainment of the circadian clock (6).Intraperitoneal injection of amino acids combined with glucose delayed the phase of the liver clock as similar as the effect of delayed feeding (9). l-carnosine is a dipeptide of the amino acids b-alanine and l-histidine, which is identified to be related with various physiological alterations (including blood glucose, blood pressure etc.) through the autonomic nerves. Bilateral lesions of the SCN in rat results in destructive effects on the carnosine induced physiological alterations mentioned above (10). In our study, we found that l-carnosine administration could accelerate the resetting rate of peripheral clock genes in the hearts, which is regulated by the autonomic nervous system (11).Alcohol is another entraining factor for circadian clocks. Chronic alcohol administration induced the hepatic steatosis and disturbed the circadian clocks in the liver (12). Studies in human indicated that the expression level of clock genes in leukocytes of male alcoholic patients were lower than the healthy men (13). Timed Nutrients and Circadian RhythmsTimed nutrients are as impor...

Circadian clock plays an essential role in orchestrating daily physiology, and its disruption can evoke metabolic diseases such as obesity. L-Carnitine can reduce blood lipid levels, and ameliorate fatty liver through regulating lipid metabolism. However, whether L-Carnitine administration may affect the disturbance of lipid metabolism and circadian rhythm of mice induced by prolonged circadian disruption is still unknown. Herein, we investigated the effects of L-Carnitine on conditions of circadian clock and lipid metabolism through a chronic jet-lag mice model which was developed by reversing 12 h light/12 h dark cycle every 4 days for a continuous 12 weeks. Results showed that L-Carnitine administration significantly decreased levels of serum glutamic-oxaloacetic transaminase (GOT) and triglycerides (TG), which were remarkably elevated by chronic jet-lag. More importantly, quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that L-Carnitine supplementation would effectively counteract the negative alterations in gene expression which related to lipid metabolism (Srebp1, Acaca, Fasn, and Scd1), metabolic regulator (mTOR) and circadian rhythm (Bmal1, Per1, Cry1 and Dec1) in the liver of mice subjected to the chronic jet-lag. As a conclusion, L-Carnitine was partly effective in preventing the disruption of circadian clock and lipid metabolic disorders induced by the chronic jet-lag.

Synchrony between circadian and metabolic processes is critical to the maintenance of energy homeostasis. Studies on essence of chicken (EC), a chicken meat extract rich in proteins, amino acids and peptides, showed its effectiveness in alleviating fatigue and promoting metabolism. A recent study revealed that it facilitated the re-entrainment of clock genes (Bmal1, Cry1, Dec1, Per1 and Per2) in the pineal gland and liver in a rat model of circadian disruption. Here, we investigated the role of EC-facilitated circadian synchrony in the maintenance of the energy homeostasis using a mouse model of prolonged circadian disruption. Prolonged circadian disruption (12 weeks) resulted in hepatic maladaptation, manifested by a mild but significant (p < 0.05) hepatomegaly, accompanied by disturbed hepatic lipid metabolism and liver injury (indicated by increased circulating hepatic enzymes). Evidently, there was marked elevations of hepatic inflammatory mediators (interleukin-1beta and interleukin-6), suggesting an underlying inflammation leading to the hepatic injury and functional impairment. Importantly, the disruption paradigm caused the decoupling between key metabolic regulators (e.g. mTOR and AMPK) and hepatic clock genes (Per1, Cry1, Dec1, Bmal1). Further, we showed that the loss of circadian synchrony between the master and hepatic clock genes (Per1, Cry1, Dec1, Bmal1) could be the underlying cause of the maladaptation. When supplemented with EC, the functional impairment and inflammation were abolished. The protective effects could be linked to its effectiveness in maintaining the synchrony between the master and hepatic clocks, and the resultant improved coupling of the circadian oscillators (Per1, Cry1, Dec1, Bmal1) and metabolic regulators (mTOR, AMPK). Overall, EC supplementation promoted the physiological adaptation to the prolonged circadian disruption through facilitation of endogenous circadian synchrony and the coupling of circadian oscillators and metabolic regulators. This forms an important basis for further elucidation of the physiological benefits of EC-facilitated circadian synchrony.