Volume 30, Issue 169, March 2026

Circadian rhythm disorders and metabolic diseases - current state of knowledge

Kamila Kałamarz^1♦, Maja Kondratowicz², Aleksandra Figzał³, Kinga Żmuda⁴, Maciej Świerczyna⁵, Maja Czerniachowska⁶, Marcin Kaniewski⁷, Martyna Wojnowska⁸, Wiktoria Polkowska⁹, Michał Grabek¹⁰

¹Karol Marcinkowski University Hospital, Zyty 26, 65-046 Zielona Góra, Poland
²The Independent Public Hospital No. 4, Lublin, Poland
³Karol Marcinkowski University Hospital, Zyty 26, 65-046 Zielona Góra, Poland
⁴University Clinical Hospital of Opole al.W.Witosa 26 45-401 Opole, Poland
⁵Ministry of the Interior and Administration Hospital, Północna 42, 91-425 Łódź, Poland
⁶Medical University of Łódź, al. Kościuszki 4, 90-419 Łódź, Poland
⁷The Independent Public Hospital No. 4, Lublin, Poland
⁸Mikolaj Pirogov Provincial Specialist Hospital, Wólczańska 191/195, 90-001 Łódź, Poland
⁹Central Clinical Hospital, Medical University of Łódź, Pomorska 251, 90-213 Łódź, Poland
¹⁰Karol Marcinkowski University Hospital, Zyty 26, 65-046 Zielona Góra, Poland

^♦Corresponding author
Kamila Kałamarz, Karol Marcinkowski University Hospital, Zyty 26, 65-046 Zielona Góra, Poland

ABSTRACT

A complex TTFL underlies circadian rhythms of transcription and translation (TTFL), which acts as the main molecular oscillator in cells. This system has two parts. Firstly, there are positive regulatory elements, which include the heterodimeric transcription factors CLOCK and BMAL1. These activate the expression of core clock genes and their protein products. Secondly, a delayed negative feedback mechanism is in place, in which protein products e.g. PER and CRY, accumulate, form complexes, and move to the nucleus to inhibit CLOCK:BMAL1 activity. This stops them making more copies of themselves. The feedback loop fluctuates. This movement takes about 24 hours to complete. This ~24-hour cycle maintains physiological homeostasis. Secondly, we have found that certain proteins (nuclear receptors) work together to control the rhythm of the clock genes, making them more stable and efficient. Clock-controlled genes regulate key processes (e.g., metabolism) via rhythmic expression. This is because these genes are aligned with time-of-day cues. The accuracy of the molecular clock pauses ensures pauses in various processes, including transcription, translation, protein synthesis and breakdown, as well as post-translational modifications e.g., phosphorylation. This architecture elucidates clock disruption effects. This is because it helps us to understand how disruptions to the body's clock affect metabolic diseases. It also helps us develop ways to treat metabolic health problems based on the patient's circadian rhythm.

Keywords: Circadian rhythm, metabolic diseases, diabetes, obesity, chronotherapy, metabolism

Medical Science, 2026, 30, e46ms3793

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DOI: https://doi.org/10.54905/disssi.v30i169.e46ms3793

Published: 03 March 2026