An essential regulatory arm of the biological clock, involved in metabolic and circadian rhythms regulation.
Circadian clock proteins act as transcription factors controlling genes of the immune system. Circadian clock proteins engage in direct physical interactions with inflammatory proteins. Immune factors also reciprocally exert control over circadian clock function. Circadian clock genes are expressed and oscillate in many cell types such as macrophages, neurons, and pancreatic β cells. During inflammation, these endogenous clocks control the temporal gating of cytokine production, the antioxidant response, chemokine attraction, and insulin secretion, among other processes.
Variations in clock genes in macrophages or brain-resident cells induce a higher production of inflammatory cytokines and chemokines, and this is often accompanied by increased oxidative stress. In the context of obesity and diabetes, a high-fat diet disrupts the function of clock genes in macrophages and in pancreatic β cells, contributing to inflammation and systemic insulin resistance. Recently, it has been shown that the administration of natural and synthetic ligands or pharmacological enhancers of the circadian clock function can selectively regulate the production and release of pro-inflammatory cytokines and improve the metabolic function in vitro and in vivo. Thus, a better understanding of the circadian regulation of the immune system could have important implications for the management of metabolic and neurodegenerative diseases.
A diet high in fat can down-regulate CLOCK function.
A C-allele in this gene may be associated with behavioural changes in certain populations and with obesity and metabolic syndrome.