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Study links circadian rhythm disruption to obesity and diabetes
Last reviewed: 02.07.2025
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A new study published in the Journal of Clinical Investigation reviewed evidence of circadian rhythm disruption, metabolic health, and circadian locomotor output (clock) cycle genes.
Daily routines of life are linked to the environment, leading to the evolution of circadian rhythms. Cues such as temperature, sunlight, food, and sound, called "zeitgebers," adapt circadian rhythms to external conditions. Growing evidence links circadian disruptions or zeitgebers to adverse human outcomes. A comprehensive review of the relationship between metabolic health and circadian gene expression is lacking. This study summarized and compared evidence from animal models with epidemiological data to improve understanding of the contribution of circadian disruptions and clock gene expression to metabolic health-related pathologies.
Circadian rhythms in animal models
Genetic drivers of circadian rhythms in animals were first discovered in the fruit fly Drosophila melanogaster, which showed that the period gene (per) and protein (PER) were important for circadian rhythm. Further studies confirmed these results and identified additional key clock genes, such as brain and muscle ARNT-like 1 (BMAL1), cryptochrome (CRY), and PER orthologs (PER1–PER3).
Mice with mutated clock genes showed altered meal times and consumed more calories, leading to metabolic syndrome and obesity, as well as a decreased activity rhythm. Similar metabolic changes have been noted in other mouse models with mutations in molecular clock components.
Glucose homeostasis and gene expression
Glucose homeostasis is regulated by specific gene signaling mechanisms controlled by certain CCGs. The study showed that in mice with normal BMAL1 expression in pancreatic β-cells, BMAL1/CLOCK dimers bound to regulatory sites, leading to transcription of targets other than liver cells. Mice with impaired BMAL1 expression developed glucose intolerance.
Epidemiological and population studies
Preliminary evidence from epidemiological analyses of night shift workers suggests that metabolic health is altered by circadian disruption. The Nurses' Health study noted that participants who worked night shifts had increased caloric intake, shortened sleep duration, and were more likely to be obese.
CCG gene expression and circadian disruption
A study of 18 nurses found that shift workers had fewer rhythmic genes in their peripheral blood mononuclear cells than day shift workers. Another study of 60 nurses found differential expression of nearly all CCGs. In a separate study, 22 participants were subjected to forced desynchronization of 28-hour days, with sleep onset shifted by four hours each night.
Metabolic pathology and CCG genes
There may be a bidirectional relationship between CCG expression and metabolic health, as worsening metabolic health may alter CCG expression in a tissue-specific manner. One study of 28 obese and 21 lean women without diabetes showed altered expression of various CCGs in obese individuals.
Conclusion
A growing body of evidence links clock gene activity to pathological metabolic outcomes. The impact of circadian disruptors depends on the duration and quality of exposure. Long periods of shift work may prevent internal organs from restoring normal rhythms. Additional research is needed to deepen the evidence base and improve understanding of these relationships.