A biological rhythm in the hypothalamic system links sleep-wake cycles with feeding-fasting cycles

Abstract

Abstract The hypothalamus senses the appetite-regulating hormones and also coordinates the metabolic function in alignment with the circadian rhythm. This alignment is essential to maintain the physiological conditions that prevent clinically important comorbidities, such as obesity or type-2 diabetes. However, a complete model of the hypothalamus that relates food intake with circadian rhythms and appetite hormones has not yet been developed. In this work, we present a computational model that accurately allows interpreting neural activity in terms of hormone regulation and sleep-wake cycles. We used a conductance-based model, which consists of a system of four differential equations that considers the ionotropic and metabotropic receptors, and the input currents from homeostatic hormones. We proposed a logistic function that fits available experimental data of insulin hormone concentration and added it into a short-term ghrelin model that served as an input to our dynamical system. Our results show a double oscillatory system, one synchronized by light-regulated sleep-wake cycles and the other by food-regulated feeding-fasting cycles. We have also found that meal timing frequency is highly relevant for the regulation of the hypothalamus neurons. We therefore present a mathematical model to explore the plausible link between the circadian rhythm and the endogenous food clock.

Keywords

• Sleep-wake cycle
• Feeding-fasting cycle
• Melanocortin system
• Circadian rhythm
• Obesity
• Diabetes