Neuroendocrine modulation of food reward in binge eating: Insulin sensitivity has dissociable effects on insular food-reward signals in binge eating

Abstract

Our society faces ever-increasing rates of obesity and type 2 diabetes mellitus, associated with increased healthcare costs and mortality rates, and eating disorders are a major contributor. This also includes binge eating disorder (BED), which, after being recognized as a single clinical diagnosis in 2013, turned out to be the most common eating disorder. Research on the mechanisms of genesis and maintenance is correspondingly young and mainly deals with the processing of food stimuli in dopaminergic reward centers. Previously, it was assumed that decreased peripheral insulin sensitivity contributes to altered signaling in neuronal centers, as it has been shown that many insulin receptors are expressed in areas affecting motivation, food anticipation and reward. This has not yet been studied in people with BED. Here, we investigated associations between symptoms of binge eating, peripheral insulin sensitivity, and neural FCR in 61 participants (Mage = 39.7 years ± 13.2; MBMI = 31.5 kg/m2 ± 7.1 [20.2, 46]; MWtHR = 0.57 ± 0.1 [0.4, 0.7]) who were divided into 3 groups (NBED=21, NsubBED=20, NnoBE=20). In line with previous results, we found that binge eating is associated with a greater FCR in mesocorticolimbic regions that have been linked to food reward and insulin sensitivity (i.e., insula, striatum, VTA, amygdala, OFC). Contrary to expectation, BED was not associated with higher peripheral insulin resistance or subjective hunger/fullness. Interestingly, increased HOMA-IR was associated with multiple neuronal alterations affecting the insula: HOMA-IR dampened FCR in insular, showed altered expression of insular insulin receptors, changed modulatory effects on functional connectivity between insula and sensori-motor areas, and we found a stronger relationship between hedonic liking ratings in FCR and primary sensori-motor areas. To summary, we found that both individual differences in binge eating and insulin sensitivity were associated with altered brain responses to food in the insular cortex. However, modulatory effects of HOMA-IR were co-localized with insulin receptors and largely independent of individual differences related to binge eating. Hence, our results suggest that differences in insulin sensitivity do not explain altered food reward signaling in the insular cortex of patients with BED. Our findings highlight that alterations in insulin sensitivity are unlikely to mechanistically explain the observed differences in insular food reward signals in patients with BED. Nevertheless, an improved understanding of the modulatory effects of insulin sensitivity on food reward signaling including participants with marked symptoms of binge eating may provide new avenues for the treatment of the metabolic syndrome which may help reduce negative sequelae of BED.