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 used the model to compare 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. Recently, we have analyzed global data and found evidence for a push effect in other countries and in particular developed countries. Hall and I have also shown how measurements of body mass can be used to infer food intake. The model also shows that the time scale to approach steady state when diet is changed is very long, on the order of years. This slow response may partially explain why it is so hard to maintain weight loss. People do not receive timely feedback on their diet performance. We have also resolved the long standing paradox of why body weight is maintained precisely even when food intake wildly fluctuates. We showed that the long time constant smooths the intake fluctuations and used stochastic calculus to calculate a formula. In collaboration with Boyd Swinburn and Nancy Butte, we have generalized the model to apply to growing children. In collaboration with Anne Sumner and Vipul Periwal, we 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 Vipul Periwal, we have developed a new Bayesian scheme to estimate insulin secretion. We have recently augmented the model to account for ingested meals. We have also applied the model to adolescents with Jack Yanovski.

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11
Fiscal Year
2014
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U.S. National Inst Diabetes/Digst/Kidney
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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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