The rewarding aspects of food is an important driving force mediating the decisions to seek food, including the overeating observed in many cases of obesity. In recent years, studies suggest that a lower functional dopamine system is associated with obesity. Our preliminary data suggest that the dopamine system, the central component of reward pathways, is especially important when food seeking-related energy cost is an important factor in decision to seek food. We hypothesize that individuals with lower dopaminergic function will shift their feeding behavior toward overeating when food is relatively easy to obtain. Our hypothesis would predict that lower dopaminergic function or leptin signaling deficiency in dopamine neurons can in deed cause obesity but only in an environment with abundance of low-cost and energy-rich foods, typical of the modern society. The proposed experiments are designed to test the causal link between hypo-dopaminergic activity and obesity and the hypothesized mechanisms. We will first establish whether hypo-dopaminergic activity and the hypothesized mechanisms contribute to obesity in leptin deficient mice. We will then establish whether hypo-dopaminergic activity and the hypothesized mechanisms contribute to diet-induced obesity. Lastly, we will examine gene-environment interactions in food seeking behavior and obesity. We will test whether dopamine D2 receptor deficient mice will be more susceptible and hyperdopaminergic mice will be more resistant to diet induced obesity in an environment with abundance of energy-rich foods.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
High Priority, Short Term Project Award (R56)
Project #
1R56DK088515-01
Application #
8086273
Study Section
Special Emphasis Panel (ZRG1-BDCN-T (02))
Program Officer
Yanovski, Susan Z
Project Start
2010-08-15
Project End
2011-07-31
Budget Start
2010-08-15
Budget End
2011-07-31
Support Year
1
Fiscal Year
2010
Total Cost
$384,624
Indirect Cost
Name
University of Chicago
Department
Biology
Type
Schools of Medicine
DUNS #
005421136
City
Chicago
State
IL
Country
United States
Zip Code
60637
Beeler, Jeff A; Faust, Rudolf P; Turkson, Susie et al. (2016) Low Dopamine D2 Receptor Increases Vulnerability to Obesity Via Reduced Physical Activity, Not Increased Appetitive Motivation. Biol Psychiatry 79:887-97
Beeler, Jeff A; Frazier, Cristianne R M; Zhuang, Xiaoxi (2012) Putting desire on a budget: dopamine and energy expenditure, reconciling reward and resources. Front Integr Neurosci 6:49
Beeler, Jeff A; Frazier, Cristianne R M; Zhuang, Xiaoxi (2012) Dopaminergic enhancement of local food-seeking is under global homeostatic control. Eur J Neurosci 35:146-59
Beeler, Jeff A; McCutcheon, James E; Cao, Zhen F H et al. (2012) Taste uncoupled from nutrition fails to sustain the reinforcing properties of food. Eur J Neurosci 36:2533-46