Circulating glucose levels modulate neural control of desire for high-calorie foods in humans
Kathleen A. Page, … , Robert S. Sherwin, Rajita Sinha
Kathleen A. Page, … , Robert S. Sherwin, Rajita Sinha
Published September 19, 2011
Citation Information: J Clin Invest. 2011;121(10):4161-4169. https://doi.org/10.1172/JCI57873.
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Research Article Metabolism

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

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.

Authors

Kathleen A. Page, Dongju Seo, Renata Belfort-DeAguiar, Cheryl Lacadie, James Dzuira, Sarita Naik, Suma Amarnath, R. Todd Constable, Robert S. Sherwin, Rajita Sinha

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Figure 1

Study procedure.

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Study procedure. (A) While subjects were in the scanner, a hyperinsuline...
(A) While subjects were in the scanner, a hyperinsulinemic clamp was performed with a constant infusion of insulin along with variable amounts of glucose to maintain euglycemic conditions for the first 60 minutes. For the stepped clamp study (n = 14), plasma glucose was then lowered to approximately 65 mg/dl for the hypoglycemic phase. For the euglycemic control study (n = 7), plasma glucose was maintained at approximately 90 mg/dl (dotted line). During both conditions, functional scans were performed while subjects viewed images that were projected onto a screen in the scanner. (B) Time course of a single trial. Each trial consisted of 3 events. First, a high-calorie food, low-calorie food, or non-food picture appeared for 6 seconds. Second, two rating scales were presented for 3 seconds each and consisted of liking and wanting scales with values 1–9, where a rating of 1 indicated “not at all” and a rating of 9 indicated “very much.” At the end of a trial, a fixation cross appeared, and subjects relaxed until the onset of the next trial.