Abstract
The mouse has become the most popular organism for investigating molecular mechanisms of body weight regulation. But understanding the physiological context by which a molecule exerts its effect on body weight requires knowledge of energy intake, energy expenditure, and fuel selection. Furthermore, measurements of these variables made at an isolated time point cannot explain why body weight has its present value since body weight is determined by the past history of energy and macronutrient imbalance. While food intake and body weight changes can be frequently measured over several weeks (the relevant time scale for mice), correspondingly frequent measurements of energy expenditure and fuel selection are not currently feasible. To address this issue, we developed a mathematical method based on the law of energy conservation that uses the measured time course of body weight and food intake to estimate the underlying continuous-time dynamics of energy output and net fat oxidation. We applied our methodology to male C57BL/6 mice consuming various ad libitum diets during weight gain and loss over several weeks and present the first continuous-time estimates of energy output and net fat oxidation rates underlying the observed body composition changes. We show that transient energy and fat imbalances in the first several days following a diet switch can account for a significant fraction of the total body weight change. We also discovered a time-invariant curve relating body fat and fat-free masses in male C57BL/6 mice, and the shape of this curve determines how diet, fuel selection, and body composition are interrelated.
Highlights
Mouse models of obesity have become critically important research tools for discovering molecular mechanisms of body weight regulation
We present a mathematical method that quantitatively relates food intake, body weight and body fat to calculate the dynamic changes of energy output and net fat oxidation rates during the development of obesity and weight loss in male C57BL/6 mice
The unrelenting obesity epidemic has resulted in intensive basic scientific investigation into the molecular mechanisms of body weight regulation—with the mouse being the organism of choice for such studies
Summary
Mouse models of obesity have become critically important research tools for discovering molecular mechanisms of body weight regulation. Understanding these mechanisms in the context of whole-body physiology requires knowledge of food intake, energy output, and fuel selection [1]. While food intake and body weight changes can be measured frequently over several weeks (the relevant time scale for mice), correspondingly frequent measurements of energy output and fuel selection are not currently feasible. Expensive indirect calorimetry systems can be used to measure energy expenditure and respiratory exchange over periods of a few days and most systems require removing mice from their normal environment which can alter their behavior [3]. Significant quantities of blood need to be collected which could impact the behavior of the mouse and makes repeat measurements untenable [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
