Biophysics Group, Institute of Physics, University of Antioquia, Medellin, Colombia.
Grupo de Fundamentos y Enseñanza de la Física y los Sistemas Dinámicos, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Medellin, Colombia.
Sci Rep. 2024 Nov 21;14(1):28897. doi: 10.1038/s41598-024-77915-4.
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.
下丘脑感知食欲调节激素,并与昼夜节律协调代谢功能。这种协调对于维持生理状态至关重要,可预防肥胖或 2 型糖尿病等临床上重要的合并症。然而,尚未建立将食物摄入与昼夜节律和食欲激素联系起来的完整下丘脑模型。在这项工作中,我们提出了一个计算模型,该模型可以准确地根据激素调节和睡眠-觉醒周期来解释神经活动。我们使用基于电导率的模型,该模型由四个微分方程系统组成,考虑了离子型和代谢型受体以及来自稳态激素的输入电流。我们提出了一个逻辑函数,该函数适合胰岛素激素浓度的可用实验数据,并将其添加到短期胃饥饿素模型中,作为我们动力系统的输入。我们的结果显示出一个双振荡系统,一个由光调节的睡眠-觉醒周期同步,另一个由食物调节的进食-禁食周期同步。我们还发现,用餐时间频率对下丘脑神经元的调节非常重要。因此,我们提出了一个数学模型来探索昼夜节律与内源性食物钟之间的可能联系。