The connections between circadian rhythmicity and health outcomes are abundant and are being studied around the world. It is evident that the body’s internal circadian clock plays a pivotal role in health, with growing evidence highlighting its significance in both the development and treatment of diseases. Today, we are going to take a closer look at the intersection of circadian rhythmicity and metabolic diseases.
What are metabolic diseases?
Metabolic diseases encompass a range of disorders that disrupt the body’s ability to process nutrients and energy efficiently. These conditions, including diabetes, obesity, and certain inherited metabolic disorders.
The influence of circadian rhythms on health and disease becomes more apparent as research uncovers links between disruptions in these internal biological cycles and various illnesses. Deviations in sleep patterns, exposure to shift work, or other environmental factors that disrupt these rhythms are associated with metabolic disorders such as obesity and insulin resistance. A 2008 study by Scott et al., identified a connection between changes or mutations of one of the main circadian genes, called “CLOCK” gene and the development of diabetes in humans. This genetic variation is linked to differing prevalence rates of obesity, type 2 diabetes, and cardiovascular disease, depending on the specific haplotype. Disruptions in circadian rhythm caused by a change in this gene can impact various metabolic processes, including glucose metabolism and insulin sensitivity, which are central to the development of diabetes (Scott et al., 2008).
Circadian Control of Metabolism
Glucose and Lipid Metabolism:
Circadian rhythms regulate the expression and activity of important functions involved in glucose and lipid metabolism. For instance, insulin sensitivity and glucose tolerance exhibit circadian variation, with peak sensitivity typically aligned with the active phase of the day. Similarly, lipid synthesis, storage, and mobilization follow circadian patterns, with lipogenesis being more active during periods of feeding and lipolysis predominating during fasting or rest phases. These fluctuations in metabolic processes help to synchronize energy utilization with nutrient availability, optimizing metabolic efficiency (Pan et al., 2020).
Appetite Regulation:
Circadian rhythms also influence appetite regulation and feeding behavior through the modulation of hunger and satiety signals. Hormones can exhibit circadian variations, influencing feelings of hunger and fullness. The timing of food intake, synchronized with circadian cues such as light-dark cycles and meal timing, further regulates appetite and metabolic responses to nutrient intake.
Energy Expenditure:
Circadian rhythms modulate energy expenditure through the regulation of metabolic rate, thermogenesis, and physical activity. Core body temperature, which follows a circadian pattern with a trough during sleep and peak during wakefulness, influences metabolic rate and energy expenditure. Additionally, circadian control of locomotor activity and rest-activity cycles dictates the timing and intensity of energy expenditure throughout the day, contributing to overall energy balance.
Time Restricted Feeding
Time-restricted feeding (TRF) is a dietary approach that restricts the timing of food intake to certain hours of the day. Usually this falls within a specific window, such as an 8- to 12-hour period. This strategy aligns with our circadian rhythms, aiming to optimize metabolic health. Studies show that this dietary approach may improve various metabolic parameters, including glucose metabolism, insulin sensitivity, and lipid profiles. TRF seems also to support weight management efforts by promoting more consistent energy balance throughout the day and reducing the likelihood of overeating during late-night hours. However, further research is needed to fully understand the long-term effects and optimal implementation of TRF approach for metabolic health and disease prevention.
Written by Katie Goddard
References
Scott, E., Carter, A. & Grant, P. Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man. Int J Obes 32, 658–662 (2008). https://doi.org/10.1038/sj.ijo.0803778
Valladares, M., Obregón, A. M., & Chaput, J. P. (2015). Association between genetic variants of the clock gene and obesity and sleep duration. Journal of physiology and biochemistry, 71(4), 855–860. https://doi.org/10.1007/s13105-015-0447-3
Pivovarova-Ramich, O., Zimmermann, H. G., & Paul, F. (2023). Multiple sclerosis and circadian rhythms: Can diet act as a treatment?. Acta physiologica (Oxford, England), 237(4), e13939. https://doi.org/10.1111/apha.13939
Pan, X., Mota, S., & Zhang, B. (2020). Circadian Clock Regulation on Lipid Metabolism and Metabolic Diseases. Advances in experimental medicine and biology, 1276, 53–66. https://doi.org/10.1007/978-981-15-6082-8_5
Gooley J. J. (2016). Circadian regulation of lipid metabolism. The Proceedings of the Nutrition Society, 75(4), 440–450. https://doi.org/10.1017/S0029665116000288
de Assis, L. V. M., & Oster, H. (2021). The circadian clock and metabolic homeostasis: entangled networks. Cellular and molecular life sciences : CMLS, 78(10), 4563–4587. https://doi.org/10.1007/s00018-021-03800-2