33.3 Insulin and Glucose Manipulations Affecting Mesolimbic and Prefrontal Circuits Underlying Wanting of High-reward Foods: Implications for Obesity
University of Southern California School of Medicine, Los Angeles, California
Background: Obesity is a worldwide epidemic resulting in part from the ubiquity of high-calorie foods and food images. In a series of studies, we have shown how metabolic signals such as glucose and insulin influence brain pathways that regulate the motivation to consume high-calorie foods.
Methods: Using functional magnetic resonance imaging combined with blood sampling we examined brain, hormonal and behavioral measures of appetite and food motivation in obese and lean volunteers: 1) under euglycemia vs mild hypoglycemia using a stepped hyperinsulinemic, euglycemic-hypoglycemic clamp; 2) after an acute consumption of glucose or fructose alone; and 3) after glucose or fructose consumption in combination with exposure to high-calorie food cues.
Results: Mild hypoglycemia preferentially activated limbic-striatal brain regions in response to food cues to produce a greater desire for high-calorie foods. In contrast, euglycemia preferentially activated the medial prefrontal cortex (mPFC), an executive control region, and resulted in less interest in food stimuli. Higher circulating glucose levels predicted greater mPFC activation. The prefrontal cortex response was absent in obese individuals. Consumption of glucose, but not fructose, deactivated hypothalamic and striatal regions and increased satiety. In contrast, consumption of fructose compared to glucose resulted in greater food-cue reactivity in the nucleus accumbens and greater desire for food. Circulating levels of glucose and insulin were significantly higher after glucose vs. fructose consumption, and higher insulin levels predicted greater mPFC activation to food cues after glucose consumption.
Conclusions: These findings demonstrate a role for circulating glucose and insulin in modulating neural control over food motivation and suggest a loss of the glucose-linked restraining influence in obesity. Differential brain, hormonal and appetitive responses to fructose compared to glucose consumption may promote overeating behavior.
Disclosure: Nothing to Disclose.