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[Meal timing and dysregulation of metabolic systems such as obesity have a close association, especially among shift workers. The circadian regulation on nutrient metabolic systems in animals is now under discussion. In a previous experimental study, they found that food intakes in the resting time in their rat model cause more fat gain than food intakes in the active time. In this study, we aim to elucidate the mechanism of the circadian regulation of glucose metabolism in the liver. We developed a simple mathematical model describing the glucose allocation process into glycogen and fat, considering the circadian regulation on glycogenesis, glycogenolysis, and fat synthesis. We predicted that more fat production from food intake in the resting time than active time was realized when the peak time of fat synthesis is in the resting time. Next, considering phase shifts of glycogenesis and fat synthesis, we calculated two types of possible metabolic dysfunctions: (Acosta-Rodríguez VA, de Groot MHM, Rijo-Ferreira F, Green CB, Takahashi JS (2017) Mice under caloric restriction self-impose a temporal restriction of food intake as revealed by an automated feeder system. Cell Metab 26(1):267–277.e2) high blood glucose and (Adamovich Y, Rousso-Noori L, Zwighaft Z, Neufeld-Cohen A, Golik M, Kraut-Cohen J, Wang M, Han X, Asher G (2014) Circadian clocks and feeding time regulate the oscillations and levels of hepatic triglycerides. Cell Metab 19(2):319–330.) energy exhaustion. We found that the condition with fat synthesis peak in the resting time achieved less energy exhaustion, which is revealed to be beneficial in terms of homeostasis of the energy supply. Our model is the first step to understand the dynamic circadian regulation of glucose metabolism. It will be useful to propose the optimal meal schedule to prevent metabolic diseases caused by the irregular meal timing in modern society.]
Published: Sep 11, 2022
Keywords: Mathematical model; Chronobiology; Circadian rhythm; Nutrient metabolism
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