The Effect of Insulin Sensitivity on Corticolimbic Responses to Metabolic and Visual Food Cues

Abstract

Insulin is one of several molecules that signals the energy balance state to the brain. This study examined the effect of insulin sensitivity on the responsiveness of appetite regulatory brain regions to visual food cues. Nineteen participants diagnosed with polycystic ovary syndrome (PCOS) were studied. Subjects were divided into insulin-sensitive (n=8) and insulin-resistant (n=11) groups based on the homeostatic model assessment of insulin resistance (HOMA2-IR). Subjects underwent functional magnetic resonance imaging (fMRI) while viewing food pictures following water or dextrose consumption. The corticolimbic Blood Oxygen Level Dependent (BOLD) responses to high-calorie (HC) or low-calorie (LC) food pictures were compared within and between groups. BOLD responses to food pictures were reduced during a glucose challenge in numerous corticolimbic brain regions of insulin-sensitive subjects, but not in insulin-resistant subjects. In addition, a positive interaction was detected between insulin sensitivity and condition. Furthermore, the degree of insulin resistance positively correlated with the corticolimbic BOLD response in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate and ventral tegmental area (VTA) in response to HC pictures and in the dorsolateral prefrontal cortex (DLPFC), mPFC, anterior cingulate, and insula in response to LC pictures following a glucose challenge. The activity in the OFC, midbrain, hippocampus, and amygdala was positively correlated with HOMA2-IR in response to HC>LC pictures following a glucose challenge. We conclude that the normal inhibition of corticolimbic brain responses to food pictures during a glucose challenge is compromised in insulin-resistant subjects. The increase in brain responsiveness to food pictures during postprandial hyperinsulinemia may lead to greater non-homeostatic eating and perpetuate obesity in insulin-resistant subjects. Understanding how insulin sensitivity affects appetite-regulating brain regions responses to food pictures is necessary for the development of prevention strategies and effective therapeutic targets for the treatment of obesity, particularly obesity related to insulin resistance in PCOS.