Circulating glucose levels modulate neural control of desire for high-calorie foods in humans

TLDR

Obesity worldwide is driven in part by the ubiquity of high‑calorie foods and food images, yet it remains unclear whether obese and non‑obese people differ in how they regulate their desire for such foods. The study tested whether circulating glucose levels modulate brain regions that control motivation to consume high‑calorie foods. Functional MRI during a glucose clamp showed that mild hypoglycemia preferentially activates limbic‑striatal circuits to heighten desire for high‑calorie foods, whereas euglycemia engages the medial prefrontal cortex to dampen interest; higher glucose predicted stronger medial prefrontal activation, a response absent in obese subjects, indicating that glucose‑linked restraint on food motivation is lost in obesity and suggesting that strategies to prevent postprandial glucose dips could reduce overeating.

Abstract

Obesity is a worldwide epidemic resulting in part from the ubiquity of high-calorie foods and food images. Whether obese and nonobese individuals regulate their desire to consume high-calorie foods differently is not clear. We set out to investigate the hypothesis that circulating levels of glucose, the primary fuel source for the brain, influence brain regions that regulate the motivation to consume high-calorie foods. Using functional MRI (fMRI) combined with a stepped hyperinsulinemic euglycemic-hypoglycemic clamp and behavioral measures of interest in food, we have shown here that mild hypoglycemia preferentially activates 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 and resulted in less interest in food stimuli. Indeed, higher circulating glucose levels predicted greater medial prefrontal cortex activation, and this response was absent in obese subjects. These findings demonstrate that circulating glucose modulates neural stimulatory and inhibitory control over food motivation and suggest that this glucose-linked restraining influence is lost in obesity. Strategies that temper postprandial reductions in glucose levels might reduce the risk of overeating, particularly in environments inundated with visual cues of high-calorie foods.