Cognitive impairment with diabetes mellitus and metabolic disease: innovative insights with the mechanistic target of rapamycin and circadian clock gene pathways.
This perspective focuses on the relationship of circadian clock genes with oxidative stress, inflammatory response, and metabolic disorders and emphasizes the regulation of phytochemicals on the circadian clock.
At the same time, a variety of conditions including metabolic disorders also impact clock gene expression, resulting in circadian disruptions, which in turn often exacerbates the disease state.
A variety of metabolic activities are under circadian modulation, as local and global clock gene knockouts result in glucose imbalance and increased risk of metabolic diseases.
Additionally, the critical role of the rhythmic methylation pattern of clock genes in battery of cancer and metabolic disorders also defines its importance.
Based on genetic models with mutation or deletion of core clock genes, circadian disruption has been implicated in the pathophysiology of metabolic disorders.
Furthermore, exposure to a high-fat diet also disrupts normal circadian rhythms, and conversely, clock gene knockout models have symptoms of metabolic disorders.
Mice lacking TrpV1 become more obese and develop insulin resistance when fed with high fat diet; however, a relationship between metabolic disorders, TRP channels, and clock genes is still unknown.
A series of our recent studies revealed that circadian clock proteins are important for hypofibrinolysis induced by metabolic disorders such as obesity and diabetes.