Juen Guo, Ph.D.
- Ph.D., University of Maryland, 2005
- M.S., China Agricultural University, 2000
Our goal is to develop mathematical models that quantify the dynamic fluxes of energy metabolites during obesity development and weight loss periods in rodents. The models would also predict energy intake, body weight, and composition under various dietary circumferences.
Obesity, once established, is difficult to reverse in humans. My research team completed a feeding study in C57BL/6 mice and found that obesity arising from temporary exposure to obesigenic diets led to a persistent state of obesity after the obesigenic diet was removed. Qualitatively, it is clear that obesity results from a prolonged period where food intake exceeds energy expenditure. However, researchers have not been able to clearly and quantitatively integrate data on various aspects of energy metabolism, food intake, and body composition changes to better understand the mechanisms responsible for the development and persistence of obesity. My research is focused on building mathematical models of energy metabolism and body composition dynamics in C57BL/6 mice. I developed a novel computational methodology to demonstrate how energy intake, energy expenditure, and fuel selection are interrelated and give rise to observed changes in body weight and body composition in lab mice. Based on this methodology, I developed a mathematical model that predicts the changes of body weight and composition in lab mice, given their food composition and energy intake. Such a model helps us to better understand our own data on body weight regulation in lab mice. It will also serve as a general utility for other investigators studying various mouse models of body weight regulation.
Applying our Research
The current epidemic of obesity has profound public health implications. Obesity results from an imbalance between the energy derived from food and the energy expended to maintain life and perform work. This energy balance concept has been the cornerstone of nutrition research for more than a century. An updated and more specific version of the energy balance concept states that changes in body fat and lean masses are related to imbalances between the intake, oxidation, and inter-conversion of carbohydrate, fat, and protein. Because it is extraordinarily difficult to measure these variables in free-living humans, and because human obesity develops over many years, mouse models have become a popular tool for the investigation of energy balance and body composition regulation, as well as the development and treatment of obesity. But despite the popularity of such mouse models, there is no available technology to quantitatively integrate food intake, body composition, energy expenditure, and macronutrient oxidation data in mice. Without such a technology, it is extraordinarily difficult to understand the relative importance of food intake versus energy expenditure or macronutrient oxidation in determining body composition changes. This project will develop such a technology.
Need for Further Study
The proposed models will be vigorously evaluated with the latest data from published studies to identify weaknesses and to make improvements accordingly. Presently, the proposed model does not explicitly include the effects of hormones and obesity-related genes, although these are implicitly included in the model parameters. Future work will explicitly account for those effects and will extend the model to rats and other strains of mice. Such a model could be used to compare experiment results between mice and rats, or even between different mouse strains and genetically-engineered animal models.
- Heritability and genetic correlations explained by common SNPs for metabolic syndrome traits.
- Vattikuti S, Guo J, Chow CC.
- PLoS Genet (2012) 8:e1002637. Abstract/Full Text
- Challenges of indirect calorimetry in mice.
- Guo J, Hall KD.
- Am J Physiol Regul Integr Comp Physiol (2011 Mar) 300:R780; author reply R781-2. Abstract/Full Text
Research in Plain Language
I use computer models and laboratory experiments to study how mice use energy to help regulate weight. This research will help us better understand how to treat or prevent obesity in humans.