Jennifer Leohr(1), and Maria C. Kjellsson(2)
(1) Pharmacokinetics/Pharmacodynamics and Pharmacometrics, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 462852 (2)Pharmacometrics Research Group, Department of Pharmaceutical Biosciences, Uppsala University, Sweden.
Introduction/Objectives: Obesity is a disorder of chronic positive energy balance, whereby excess of energy intake beyond energy utilization leads to an increase in adipose tissue. Chronic over-eating leading to the development of obesity can be modeled as an addictive behavior similar to other substance disorders in which craving and reward play a key role. In a series of studies assessing hedonic response and preference for dairy solutions with varying sucrose and fat content, the degree of hedonic response elicited by preferred solutions was shown to be related to weight gain [1] and the corresponding preferred sugar to fat ratio was shown to vary with BMI [2]. The aim of this study was to assess the hedonic response to dairy solutions with variable concentrations of sucrose and fat were measured as a surrogate for sensitivity to reward and to determine relative preference for sweet and fat in normal-weight versus obese subjects.
Methods: Data was collected from a single-center, in a total of 64 subjects, roughly 20 subjects in each of the three population categories based on BMI: lean (18.5-24.9), obese (30-33), and very obese (34-40). Approximately 90 minutes following the lunch meal, subjects will undergo a sweet and fat taste preference test. For example, subjects may be presented with 16 randomly ordered solutions of skim milk (0% fat), whole milk (3.5% fat), half and half (11.3% fat) and cream (37.5% fat) each containing 0%, 5%, 10%, or 20% sugar by weight. Subjects rated solutions for sweetness, creaminess and pleasantness on three separate scales anchored with descriptors of “not at all” and “extremely.” The set of solutions were rated twice. Nonlinear mixed-effect modeling was used to model the categorical data from the scoring of the sugar/fat preference test, using NONMEM® [3] and Perl-speaks-NONMEM [4] as the modeling environment.
Results: The creaminess score was well described with a proportional odds model with linear effects of sugar and fat on the score. The sweetness score was also well described with a proportional odds model. Sugar content effects on the score was best described by an Emax model. The pleasantness score was more complex than both the sweetness and creaminess score. A differential odds model allowed for the sugar to be less than proportional and fat to be greater than proportional on the score. In addition, the sugar and fat effect on pleasantness was described by an Emax model with an estimated interaction between fat and sugar.
Conclusions: The creaminess score was unsurprisingly dependent on the content of the fat in the test. In addition, the results showed that sugar amount increased the creaminess rating. Similarly, the sweetness score was dependent on the amount of sugar with the fat content increasing the sweetness rating. Population differences were identified for the baseline of sweetness. The pleasantness score was dependent on both the amount of sugar and fat content of the test, with both showing a maximum response on the score (Emax models). The interaction between sugar and fat was negative, indicating an antagonistic interaction on the pleasantness score; thus, doubling the fat content and the sugar amount will not quadruple the pleasantness. This was also observed in the raw data where higher fat content reduced the pleasantness score for all amounts of sugar. The development of this model provides a unique opportunity to further understand these complex interaction of sugar and fat on hedonic response. In addition, this approach provides a powerful tool to conduct simulations for hypothesis testing and avoiding additional subjects enduring a tedious and time consuming test.
References:
[1]. Salbe AD, DelParigi A, Pratley RE, Drenowski A, Tataranni PA. 2004. Taste preferences and body weight changes in an obesity-prone population. Am J Clin Nutr 79:372-378.
[2]. Drewnowski A, Shrager EE, Lipsky C, Stellar E, Greenwood MRC. 1989. Sugar and fat: Sensory and hedonic Evaluation of liquid and solid foods. Physiology and Behavior 45:177-183.
[3]. Beal SL and Sheiner LB. NONMEM Users Guides. Hanover, Maryland: GloboMax, Inc., 1989–1998.
[4]. Lindbom L, Ribbing J, Jonsson EN. Perl-speaks-NONMEM (PsN)—a Perl module for NONMEM related programming. Comput Methods Programs Biomed 2004; 75(2): 85–94.
Reference: PAGE 27 (2018) Abstr 8521 [www.page-meeting.org/?abstract=8521]
Poster: Drug/Disease Modelling - Endocrine