Computational modelling of energy balance in individuals with Metabolic Syndrome

Abstract

Background A positive energy balance is considered to be the primary cause of the development of obesity-related diseases. Treatment often consists of a combination of reducing energy intake and increasing energy expenditure. Here we use an existing computational modelling framework describing the long-term development of Metabolic Syndrome (MetS) in APOE3L.CETP mice fed a high-fat diet containing cholesterol with a human-like metabolic system. This model was used to analyze energy expenditure and energy balance in a large set of individual model realizations. Results We developed and applied a strategy to select specific individual models for a detailed analysis of heterogeneity in energy metabolism. Models were stratified based on energy expenditure. A substantial surplus of energy was found to be present during MetS development, which explains the weight gain during MetS development. In the majority of the models, energy was mainly expended in the peripheral tissues, but also distinctly different subgroups were identified. In silico perturbation of the system to induce increased peripheral energy expenditure implied changes in lipid metabolism, but not in carbohydrate metabolism. In silico analysis provided predictions for which individual models increase of peripheral energy expenditure would be an effective treatment. Conclusion The computational analysis confirmed that the energy imbalance plays an important role in the development of obesity. Furthermore, the model is capable to predict whether an increase in peripheral energy expenditure – for instance by cold exposure to activate brown adipose tissue (BAT) – could resolve MetS symptoms. Electronic supplementary material The online version of this article (10.1186/s12918-019-0705-z) contains supplementary material, which is available to authorized users.

Differential microRNAs expression profiles in liver from three different lifestyle modification mice models

“…Overweight and obesity have been recognized as risk factors for many chronic diseases such as the metabolic syndrome, diabetes, and cardiovascular diseases [ 1 ]. The main driver for weight gain is considered to be the medium or long term positive energy balance, usually through consumption of a high-fat diet (HF) [ 2 , 3 ]. Treatment of obesity therefore often consists of reducing caloric intake or promoting energy utilization to diminish the surplus of energy in the system [ 3 ].…”

“…The main driver for weight gain is considered to be the medium or long term positive energy balance, usually through consumption of a high-fat diet (HF) [ 2 , 3 ]. Treatment of obesity therefore often consists of reducing caloric intake or promoting energy utilization to diminish the surplus of energy in the system [ 3 ]. In contrast to the detrimental effects of overeating energy-dense foods, caloric restriction (CR), restricting the intake of calories without causing malnutrition, has a wide range of benefits, including promoting lifespan, decreasing the incidence of age-related diseases and extending health span as well [ 4 ].…”

Differential microRNAs expression profiles in liver from three different lifestyle modification mice models

“…Overweight and obesity have been recognized as risk factors for many chronic diseases such as diabetes, cardiovascular diseases, and the metabolic syndrome [1]. The main driver for weight gain is considered to be the medium or long term positive energy balance, usually through consumption of a high-fat diet (HF) [2,3]. Treatment of obesity is therefore often aimed at diminishing the surplus of energy in the system.…”

“…Treatment of obesity is therefore often aimed at diminishing the surplus of energy in the system. This can be accomplished by making adjustments at both sides of the equation, reducing caloric intake or promoting energy utilization [3]. In contrast to the detrimental effects of overeating energy-dense foods, caloric restriction (CR), restricting the intake of calories without causing malnutrition, has a wide range of benefits [4].…”

Differential microRNAs expression profiles in liver from three different lifestyle modification mice models

“…Treatment of obesity is therefore often aimed at diminishing the surplus of energy in the system. This can be accomplished by making adjustments at both sides of the equation, reducing caloric intake or promoting energy utilization [3]. In contrast to the detrimental effects of overeating energy-dense foods, caloric restriction (CR), restricting the intake of calories without causing malnutrition, has a wide range of bene ts [4].…”