The goal of this review was to seek a better understanding of the function and differential expression of circadian clock genes during the reproductive process. Through a discussion of how the circadian clock is involved in these steps, the identification of new clinical targets for sleep disorder-related diseases, such as reproductive failure, will be elucidated. Here, we focus on recent research findings regarding circadian clock regulation within the reproductive system, shedding new light on circadian rhythm-related problems in women. Discussions on the roles that circadian clock plays in these reproductive processes will help identify new clinical targets for such sleep disorder-related diseases.

Nonalcoholic fatty liver disease (NAFLD) is becoming a major health issue as obesity increases around the world. We studied the effect of a circadian locomotor output cycles kaput (CLOCK) mutant (Clk^Δ19/Δ19) protein on hepatic lipid metabolism in C57BL/6 Clk^wt/wt and apolipoprotein E–deficient (Apoe^−/−) mice. Both Clk^Δ19/Δ19 and Clk^Δ19/Δ19 Apoe^−/− mice developed a full spectrum of liver diseases (steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma) recognized in human NAFLD when challenged with a Western diet, lipopolysaccharide, or CoCl₂. We identified induction of CD36 and hypoxia-inducible factor 1α (HIF1α) proteins as contributing factors for NAFLD. Mechanistic studies showed that WT CLOCK protein interacted with the E-box enhancer elements in the promoters of the proline hydroxylase domain (PHD) proteins to increase expression. In Clk^Δ19/Δ19 mice, PHD levels were low, and HIF1α protein levels were increased. When its levels were high, HIF1α interacted with the Cd36 promoter to augment expression and enhance fatty acid uptake. Thus, these studies establish a regulatory link among circadian rhythms, hypoxia response, fatty acid uptake, and NAFLD. The mouse models described here may be useful for further mechanistic studies in the progression of liver diseases and in the discovery of drugs for the treatment of these disorders.

The circadian rhythm is a 24 h internal clock within the body that regulates various factors, including sleep, body temperature, and hormone secretion. Circadian rhythm disruption is an important risk factor for many diseases including neurodegenerative illnesses. The central and peripheral oscillators’ circadian clock network controls the circadian rhythm in mammals. The clock genes govern the central clock in the suprachiasmatic nucleus (SCN) of the brain. One function of the circadian clock is regulating lipid metabolism. However, investigations of the circadian regulation of lipid metabolism-associated apolipoprotein genes in the brain are lacking. This review summarizes the rhythmic expression of clock genes and lipid metabolism-associated apolipoprotein genes within the SCN in Mus musculus. Nine of the twenty apolipoprotein genes identified from searching the published database (SCNseq and CircaDB) are highly expressed in the SCN. Most apolipoprotein genes (ApoE, ApoC1, apoA1, ApoH, ApoM, and Cln) show rhythmic expression in the brain in mice and thus might be regulated by the master clock. Therefore, this review summarizes studies on lipid-associated apolipoprotein genes in the SCN and other brain locations, to understand how apolipoproteins associated with perturbed cerebral lipid metabolism cause multiple brain diseases and disorders. This review describes recent advancements in research, explores current questions, and identifies directions for future research.