Circadian Rhythm Disorder as a Factor in the Development of Metabolically Unhealthy Obesity
https://doi.org/10.31550/1727-2378-2025-24-4-79-84
Abstract
Aim. Based on the analysis of data from modern scientific literature, to demonstrate the influence of the circadian system on the function of adipose tissue and on the formation of metabolically unhealthy obesity.
Key points. The circadian system regulates metabolic processes through complex neuroendocrine pathways, affecting key cellular structures. The central and peripheral circadian rhythms adapt the functions of organs and systems to sleep/wake and nutrition/starvation cycles, making a significant contribution to maintaining the body's metabolism in a state of equilibrium. At the level of adipose tissue, the circadian system regulates lipogenesis and lipolysis, and is also involved in the secretion of adipocytokines. Circadian regulation of the activity of lipogenesis and lipolysis is carried out mainly due to the influence on the processes of gene transcription of a number of key enzymes of adipose tissue involved in both processes. Disruption of the circadian rhythm leads to metabolic, hormonal, and energy imbalances. As a result of circadian rhythm disorders, the endocrine function of adipose tissue, lipid composition and variability of blood glucose levels, as well as insulin sensitivity, change, which can lead to the development of metabolically unhealthy obesity.
Conclusion. The circadian system is the coordinator of human behavioral and physiological functions depending on the time of day. Peripheral circadian oscillators, obeying the central circadian clock, regulate metabolic processes at the level of adipose tissue, liver, kidneys, muscles, etc. The coordinated operation of this entire system ensures energy homeostasis. Circadian rhythm disorders can contribute to the development of obesity, diabetes mellitus, and diseases of the cardiovascular system and cause metabolically unhealthy obesity, while a healthy lifestyle, optimizing work schedules, and eliminating sleep disorders improve metabolic processes.
About the Authors
A. S. Ametov
Russian Medical Academy of Continuous Professional Education; Botkin Hospital
Russian Federation
Russian Federation
Moscow
A. A. Kosyan
Federal Scientific and Clinical Center for Space Medicine and Biology, Medical and Sanitary Unit No. 1; Moscow City Polyclinic No. 12
Russian Federation
Russian Federation
Moscow
References
1. Meléndez-Fernández O.H., Liu J.A., Nelson R.J. Circadian rhythms disrupted by light at night and mistimed food intake alter hormonal rhythms and metabolism. Int. J. Mol. Sci. 2023;24(4):3392. DOI: 10.3390/ijms24043392
2. Sinturel F., Petrenko V., Dibner Ch. Circadian clocks make metabolism run. J. Mol. Bio. 2020;432(12):3680–99. DOI: 10.1016/j.jmb.2020.01.018
3. Finger A.M., Dibner C., Kramer A. Coupled network of the circadian clocks: a driving force of rhythmic physiology. FEBS Lett. 2020;594(17):2734–69. DOI: 10.1002/1873-3468.13898
4. de Oliveira Melo N.C., Cuevas-Sierra A., Souto V.F., Martínez J.A. Biological rhythms, chrono-nutrition, and gut microbiota: epigenomics insights for precision nutrition and metabolic health. Biomolecules. 2024;14(5):559. DOI: 10.3390/biom14050559
5. Marcheva B., Ramsey K.M., Buhr E.D., Kobayashi Y. et al. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. J. Nature. 2010;466(7306):627–31. DOI: 10.1038/nature09253
6. Lee C.H., Murrell C.E., Chu A., Pan X. Circadian regulation of apolipoproteins in the brain: implications in lipid metabolism and disease. Int. J. Mol. Sci. 2023;24(24):17415. DOI: 10.3390/ijms242417415.PMID:38139244
7. Civelek E., Ozturk Civelek D., Akyel Y.K., Kaleli Durman D. et al. Circadian dysfunction in adipose tissue: chronotherapy in metabolic diseases. Biology (Basel). 2023;12(8):1077. DOI: 10.3390/biology12081077
8. Saran A.R., Dave S., Zarrinpar A. Circadian rhythms in the pathogenesis and treatment of fatty liver disease. Gastroenterology. 2020;158(7):1948–66.e1. DOI: 10.1053/j.gastro.2020.01.050
9. Mercadante S., Bellastella A. Chrono-endocrinology in clinical practice: a journey from pathophysiological to therapeutic aspects. Life (Basel). 2024;14(5):546. DOI: 10.3390/life14050546
10. Brown A.J., Pendergast J.S., Yamazaki S. Peripheral circadian oscillators. Yale J. Biol. Med. 2019;92(2):327–35.
11. Lekkas D., Paschos G.K. The circadian clock control of adipose tissue physiology and metabolism. Auton. Neurosci. 2019;219:66–70. DOI: 10.1016/j. autneu.2019.05.001
12. Vieira E., Merino B., Quesada I. Role of the clock gene Rev-erbα in metabolism and in the endocrine pancreas. Diabetes Obes. Metab. 2015;17(suppl.1):S106–14. DOI: 10.1111/dom.12522
13. Chan K., Wong F.S., Pearson J.A. Circadian rhythms and pancreas physiology: a review. Front. Endocrinol. (Lausanne). 2022;13:920261. DOI: 10.3389/fendo.2022.9202612022
14. Heyde I., Begemann K., Oster H. Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism. Endocrinology. 2021;162(3):bqab009. DOI: 10.1210/endocr/bqab009
15. Froy O., Garaulet M. The circadian clock in white and brown adipose tissue: mechanistic, endocrine, and clinical aspects. Endocr. Rev. 2018;39(3): 261–73. DOI: 10.1210/er.2017-00193
16. Aldhahi W., Hamdy O. Adipokines, inflammation, and the endothelium in diabetes. Curr. Diab. Rep. 2003;3(4):293–8. DOI: 10.1007/s11892-003-0020-2
17. Zhao E., Tait C., Minacapelli C.D., Catalano C. et al. Circadian rhythms, the gut microbiome, and metabolic disorders. Gastro Hep. Adv. 2022;1(1):93–105. DOI: 10.1016/j.gastha.2021.10.008
18. Shostak A., Meyer-Kovac J., Oster H. Circadian regulation of lipid mobilization in white adipose tissues. Diabetes. 2013;62(7):2195–203. DOI: 10.2337/db12-1449
19. Shostak A., Husse J., Oster H. Circadian regulation of adipose function. Adipocyte. 2013;2(4):201–6. DOI: 10.4161/adip.26007
20. Grimaldi B., Bellet M., Katada M., Astarita G. et al. PER2 controls lipid metabolism by direct regulation of PPARgamma. Cell Metab. 2010;12(5): 509–20. DOI: 10.1016/j.cmet.2010.10.005
21. Solt L.A., Wang Y., Banerjee S., Hughes T. et al. Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature. 2012;485:62–8. DOI: 10.1038/nature11030
22. Paschos G.K., Ibrahim S., Song W.L., Kunieda T. et al. Obesity in mice with adipocyte-specific deletion of clock component. Arntl. Nat. Med. 2012;18(12):1768–77. DOI: 10.1038/nm.2979
23. Delezie J., Dumont S., Dardente H., Oudart H. et al. The nuclear receptor REV-ERBalpha is required for the daily balance of carbohydrate and lipid metabolism. FASEB J. 2012;26(8):3321–35. DOI: 10.1096/fj.12-208751
24. Dollet L., Zierath J.R. Interplay between diet, exercise and the molecular circadian clock in orchestrating metabolic adaptations of adipose tissue. J. Physiol. 2019;597(6):1439–50. DOI: 10.1113/JP276488
25. Engin A. Misalignment of circadian rhythms in diet-induced obesity. Adv. Exp. Med. Biol. 2024;1460:27–71. DOI: 10.1007/978-3-031-63657-8_2
26. Tang Q., Godschall E., Brennan C.D., Zhang Q. et al. Leptin receptor neurons in the dorsomedial hypothalamus input to the circadian feeding network. Sci. Adv. 2023;9(34):eadh9570. DOI: 10.1126/sciadv.adh9570
27. Arble D.M., Vitaterna M., Turek F.W. Rhythmic leptin is required for weight gain from circadian desynchronized feeding in the mouse. PLoS One. 2011;6(9):e25079. DOI: 10.1371/journal.pone.0025079
28. Liu C., Liu Y., Xin Y., Wang Y. Circadian secretion rhythm of GLP-1 and its influencing factors. Front. Endocrinol. (Lausanne). 2022;13:991397. DOI: 10.3389/fendo.2022.991397
29. Garaulet M., Ordovás J.M., Gómez-Abellán P., Martínez J.A. et al. An approximation to the temporal order in endogenous circadian rhythms of genes implicated in human adipose tissue metabolism. J. Cell Physiol. 2011;226(8):2075–80. DOI: 10.1002/jcp.22531
30. Marot L.P., Lopes T.D.V.C., Balieiro L.C.T., Crispim C.A. et al. Impact of nighttime food consumption and feasibility of fasting during night work: a narrative review. Nutrients. 2023;15(11):2570. DOI: 10.3390/nu15112570
31. April-Sanders A.K., Rodriguez C.J. Invited commentary nutrition, obesity, and exercise. metabolically healthy obesity redefined. JAMA Netw. Open. 2021;4(5):e218860. DOI: 10.1001/jamanetworkopen.2021.8860
32. Elías-López D., Vargas-Vázquez A., Mehta R., Cruz Bautista I. et al. Natural course of metabolically healthy phenotype and risk of developing cardiometabolic diseases: a three years follow-up study. Metabolic Syndrome Study Group. BMC Endocr. Disord. 2021;21(1):85. DOI: 10.1186/s12902-021-00754-1
33. Taheri S., Lin L., Austin D., Young T. et al. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med. 2004;1(3):e62. DOI: 10.1371/journal.pmed.0010062
34. LeDuc C.A., Skowronski A.A., Rosenbaum M. The role of leptin in the development of energy homeostatic systems and the maintenance of body weight. Front. Physiol. 2021;12:789519. DOI: 10.3389/fphys.2021.789519
35. Garieva M.A., Kosyan A.A. The effect of circadian rhythm disturbance on carbohydrate metabolism and the severity of obesity in patients with type 2 diabetes mellitus. Endocrinology: News, Opinions, Training. 2020;9(2):87–8. (in Russian). DOI: 10.33029/2304-9529-2020-9-2-87-88
36. Andriessen C., Schrauwen P., Hoeks J. The importance of 24-h metabolism in obesity-related metabolic disorders: opportunities for timed interventions. Int. J. Obes. 2021;45:479–90. DOI: 10.1038/S41366-020-00719-9
37. Sun M., Feng W., Wang F., Li P. et al. Meta-analysis on shift work and risks of specific obesity types. Obes. Rev. 2018;19(1):28–40. DOI: 10.1111/obr.12621
38. Lal H., Verma S.K., Wang Y., Xie M. et al. Circadian rhythms in cardiovascular metabolism. Circ. Res. 2024;134(6):635–58. DOI: 10.1161/CIRCRESAHA.123.323520
39. Bonham M.P., Bonnell E.K., Huggins C.E. Energy intake of shift workers compared to fixed day workers: a systematic review and meta-analysis. Chronobiol. Int. 2016;33(8):1086–100. DOI: https://doi.org/10.1080/07420528.2016.1192188
40. Rogers M., Coates A.M., Banks S. Meal timing, sleep, and cardiometabolic outcomes. Curr. Opin. Endocrine Metab. Res. 2021;18:128–32. DOI: 10.1016/j.coemr.2021.03.006
41. Sato T., Sato S. Circadian regulation of metabolism: commitment to health and diseases. Endocrinology. 2023;164(7):bqad086. DOI: 10.1210/endocr/bqad086
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Ametov A.S., Kosyan A.A. Circadian Rhythm Disorder as a Factor in the Development of Metabolically Unhealthy Obesity. Title. 2025;24(4):79-84. (In Russ.) https://doi.org/10.31550/1727-2378-2025-24-4-79-84
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