Circadian Regulatory Networks of Glucose Homeostasis and Its Disruption as a Potential Cause of Undernutrition.

ABSTRACT

The circadian clock system, an evolutionarily conserved mechanism, orchestrates diurnal rhythms in biological activities such as behavior and metabolism, aligning them with the earth's 24-hour light/dark cycle. This synchronization enables organisms to anticipate and adapt to predictable environmental changes, including nutrient availability. However, modern lifestyles characterized by irregular eating and sleeping habits disrupt this synchrony, leading to metabolic disorders such as obesity and metabolic syndrome, evidenced by higher obesity rates among shift workers. Conversely, circadian disturbances are also associated with reduced nutrient absorption and an increased risk of malnutrition in populations such as the critically ill or the elderly. The precise mechanisms of these disturbances in leading to either overnutrition or undernutrition is complex and not yet fully understood. Glucose, a crucial energy source, is closely linked to obesity when consumed excessively and to weight loss when intake is reduced, which suggests that circadian regulation of glucose metabolism is a key factor connecting circadian disturbances with nutritional outcomes. In this review, we describe how the biological clock in various tissues regulates glucose metabolism, with a primary focus on studies utilizing animal models. Additionally, we highlight current clinical evidence supporting the association between circadian disturbance and glucose metabolism, arguing that such disruption could predominantly contribute to undernutrition due to impaired efficient utilization of nutrients.