Estimating the Continuous-Time Dynamics of Energy and Fat Metabolism in Mice

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.

Serum lipid profile and hepatic evaluation in mice fed diet containing pequi nut or pulp (Caryocar brasiliense Camb.)

“…This beneficial increase in the antiathrerogenic fraction probably resulted from the monounsaturated oleic fatty acid content in pequi pulp and nut. Nevertheless, this effect of monounsaturated fat on HDL cholesterol is yet controversial since some studies have reported no effect on serum HDL-c levels due to the ingestion of monounsaturated fatty acids (GRUNDY; DENKE, 1990;PUIGGRÓS et al, 2002). However, many other studies have shown an increase in HDL-c (MATA et al, 1992;PÉREZ-JIMÉNEZ et al, 1995) corroborating the results of this study.…”

Cidea improves the metabolic profile through expansion of adipose tissue

“…2d) or a significant decrease in daily energy expenditure ((EE); Supplementary Fig. 3) 12 , although both measures tended to deviate in the energy accumulative direction. Metabolic efficiency, that is, the percentage of consumed energy incorporated into fat, was substantially higher in the aP2-hCidea mice ( Fig.…”

A mathematical model of leptin resistance

“…However, there exist a wide variety of models describing the regulations of body weight and metabolism (see [9] and the references therein, [7,24]). These models, based mainly on ordinary differential equations, consider different mechanisms of regulation such as energy use in humans [6,23,24] or in rodents [18,19]. In humans, Horgan [24] described the regulation of body weight regulated only by itself and food intake with a discrete stochastic model and concluded that body weight remains around a fixed value if the mean food intake and physical activity are constant.…”

“…In [7], Chow and Hall studied the impact of stochastic fluctuations in food intake on body weight evolution and concluded that short-term fluctuations in food intake have a limited impact on body-weight. Guo and Hall [18,19] developed an ordinary differential equation model based on laws of energy conservation to predict changes in body weight and energy expenditure, using only energy intake, and applied this model to mice.…”

“…Based on previous models of body weight dynamics in rodents [18,19], the main assumption of our model will be that leptin both up and down regulates leptin receptor expression -by positively regulating receptor degradation, and by also positively regulating receptor production. Activation of leptin receptors by leptin leads to the regulation of food intake, which influences body weight evolution.…”