In collaboration with Kevin Hall, I have been interested in modeling how the body partitions the macronutrients of the diet into lean and fat body tissue. Using empirical cross-sectional data of the relationship between fat and lean mass, we have developed an expression for how substrate utilization adapts to changes of diet, energy expenditure, and body fat so that energy imbalances produce the observed changes of body composition. The theoretical prediction matches experimental data without the use of free parameters. We also found that if body composition follows the empirical cross-sectional curve longitudinally then the body composition in a state of energy balance is not unique but could take on an infinite number of possible values. We showed the current data is insufficient to test whether or not this prediction is true. Recently we compared the total US food supply with the estimated energy expended by the population and showed that the food supply is exceeding the demand. The results predict that the US obesity epidemic is due to a """"""""push"""""""" effect of an excess supply on food leading to a progressive increase in food waste. We have also shown how measurements of body mass can be used to infer food intake. In collaboration with Anne Sumner and Vipul Periwal, I developed a time dependent mathematical model of the suppression of lipolysis by insulin. The model can be used to develop a quantitative measure for insulin's effect on serum free fatty acids akin to insulin sensitivity for glucose. We have tested 23 possible models and used Bayesian model comparison to choose the model that best balances fit to data with minimal model complexity. We were now doing experiments to validate the model and applying it to different populations. We have also used the model to compare differences in free fatty acid dynamics between white and black women. In collaboration with Stoney Simons, we developed a biophysical theory for steroid-regulated gene expression in the presence of various factors. Experiments have found that the dose-response curve for gene expression follows a first order Hill function and that factors can alter both the EC-50 and Vmax of the final product. This puts a strong constraint on the possible mechanisms. We have developed a general model involving a cascade of reactions that can predict the actions of various cofactors such as UBC-9, which is an enzyme important for sumoylation. The model may have general implications for the mechanism of gene transcription. The model can be used to predict the mechanism of cofactors and the order of action of multiple cofactors.

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2011
Total Cost
$431,245
Indirect Cost
City
State
Country
Zip Code
Katan, Martijn B; de Ruyter, Janne C; Kuijper, Lothar D J et al. (2016) Impact of Masked Replacement of Sugar-Sweetened with Sugar-Free Beverages on Body Weight Increases with Initial BMI: Secondary Analysis of Data from an 18 Month Double-Blind Trial in Children. PLoS One 11:e0159771
Li, Yanjun; Chow, Carson C; Courville, Amber B et al. (2016) Modeling glucose and free fatty acid kinetics in glucose and meal tolerance test. Theor Biol Med Model 13:8
Vandevijvere, Stefanie; Chow, Carson C; Hall, Kevin D et al. (2015) Increased food energy supply as a major driver of the obesity epidemic: a global analysis. Bull World Health Organ 93:446-56
Chow, Carson C; Hall, Kevin D (2014) Short and long-term energy intake patterns and their implications for human body weight regulation. Physiol Behav 134:60-5
Adler-Wailes, Diane C; Periwal, Vipul; Ali, Asem H et al. (2013) Sex-associated differences in free fatty acid flux of obese adolescents. J Clin Endocrinol Metab 98:1676-84
Hall, Kevin D; Butte, Nancy F; Swinburn, Boyd A et al. (2013) Dynamics of childhood growth and obesity: development and validation of a quantitative mathematical model. Lancet Diabetes Endocrinol 1:97-105
Hall, K D; Chow, C C (2013) Why is the 3500 kcal per pound weight loss rule wrong? Int J Obes (Lond) 37:1614
Weinstein, D H; deRijke, S; Chow, C C et al. (2013) A new method for determining gastric acid output using a wireless pH-sensing capsule. Aliment Pharmacol Ther 37:1198-209
Simons Jr, S Stoney; Chow, Carson C (2012) The road less traveled: new views of steroid receptor action from the path of dose-response curves. Mol Cell Endocrinol 348:373-82
Heuett, William J; Miller 3rd, Bernard V; Racette, Susan B et al. (2012) Bayesian functional integral method for inferring continuous data from discrete measurements. Biophys J 102:399-406

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