TY - JOUR
T1 - Why meals during resting time cause fat accumulation in mammals? Mathematical modeling of circadian regulation on glucose metabolism
AU - Hara, Akane
AU - Satake, Akiko
N1 - Funding Information:
This work was done by the Japan Society for the Promotion of Science Research Fellowship (DC1) and Grant-in-Aid for Japan Society for the Promotion of Science Fellows to A.H (18J20316). We are grateful to Camila Caldana, Yusuke Nakane, and Shigenobu Shibata for their helpful advice from the point of view of experimental research. We also thank Shingo Gibo, Hiroshi Ito, Gen Kurosawa, and Motohide Seki for their useful comments on mathematical modeling.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2021/9
Y1 - 2021/9
N2 - Synchronization of metabolic rhythms regulated by circadian clock and meal timing is essential for maintaining nutrient homeostasis in response to fluctuating food intake in animals. Despite numerous experimental findings on the involvement of circadian regulation of glucose and lipid metabolism, the optimal regulatory strategy for the maintenance of energy homeostasis remains poorly defined. A mathematical framework is useful to assess the circadian regulation of glycogen production/breakdown and de novo lipogenesis/lipolysis by evaluating the contribution of time of the day-dependent activation or the repression of each metabolic process in the maintenance of energy homeostasis. Here, we present a mathematical model that describes the dynamics of glycogen and triglyceride contents, two major forms of energy storage in the body that provide the fuel needed during different phases of food deprivation. By changing peak phases of glycogenesis and fat synthesis, we searched for the optimal phase set that minimizes the risks of two types of possible metabolic dysfunctions: (1) high blood glucose and (2) energy exhaustion. Based on the optimal phase set, we compared the level of fat accumulation between meal timing in the active and resting periods. Our results showed that an increased fat accumulation by food intake in the resting period can be the byproduct of minimizing energy homeostasis risks in the synchronized feeding schedule that animals adopt in nature. Our finding will be useful to schedule an optimal meal timing to prevent metabolic diseases caused by misalignment of biological and social time in modern society.
AB - Synchronization of metabolic rhythms regulated by circadian clock and meal timing is essential for maintaining nutrient homeostasis in response to fluctuating food intake in animals. Despite numerous experimental findings on the involvement of circadian regulation of glucose and lipid metabolism, the optimal regulatory strategy for the maintenance of energy homeostasis remains poorly defined. A mathematical framework is useful to assess the circadian regulation of glycogen production/breakdown and de novo lipogenesis/lipolysis by evaluating the contribution of time of the day-dependent activation or the repression of each metabolic process in the maintenance of energy homeostasis. Here, we present a mathematical model that describes the dynamics of glycogen and triglyceride contents, two major forms of energy storage in the body that provide the fuel needed during different phases of food deprivation. By changing peak phases of glycogenesis and fat synthesis, we searched for the optimal phase set that minimizes the risks of two types of possible metabolic dysfunctions: (1) high blood glucose and (2) energy exhaustion. Based on the optimal phase set, we compared the level of fat accumulation between meal timing in the active and resting periods. Our results showed that an increased fat accumulation by food intake in the resting period can be the byproduct of minimizing energy homeostasis risks in the synchronized feeding schedule that animals adopt in nature. Our finding will be useful to schedule an optimal meal timing to prevent metabolic diseases caused by misalignment of biological and social time in modern society.
UR - http://www.scopus.com/inward/record.url?scp=85112318083&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85112318083&partnerID=8YFLogxK
U2 - 10.1007/s00285-021-01645-8
DO - 10.1007/s00285-021-01645-8
M3 - Article
C2 - 34370098
AN - SCOPUS:85112318083
VL - 83
JO - Journal of Mathematical Biology
JF - Journal of Mathematical Biology
SN - 0303-6812
IS - 3
M1 - 26
ER -