Intranasal insulin enhances brain functional connectivity mediating the relationship between adiposity and subjective feeling of hunger

Abstract

Brain insulin sensitivity is an important link between metabolism and cognitive dysfunction. Intranasal insulin is a promising tool to investigate central insulin action in humans. We evaluated the acute effects of 160 U intranasal insulin on resting-state brain functional connectivity in healthy young adults. Twenty-five lean and twenty-two overweight and obese participants underwent functional magnetic resonance imaging, on two separate days, before and after intranasal insulin or placebo application. Insulin compared to placebo administration resulted in increased functional connectivity between the prefrontal regions of the default-mode network and the hippocampus as well as the hypothalamus. The change in hippocampal functional connectivity significantly correlated with visceral adipose tissue and the change in subjective feeling of hunger after intranasal insulin. Mediation analysis revealed that the intranasal insulin induced hippocampal functional connectivity increase served as a mediator, suppressing the relationship between visceral adipose tissue and hunger. The insulin-induced hypothalamic functional connectivity change showed a significant interaction with peripheral insulin sensitivity. Only participants with high peripheral insulin sensitivity showed a boost in hypothalamic functional connectivity. Hence, brain insulin action may regulate eating behavior and facilitate weight loss by modifying brain functional connectivity within and between cognitive and homeostatic brain regions.

Investigating the effect of glycaemic traits on the risk of psychiatric illness using Mendelian randomisation

“…This corresponds to data from anorexia cohorts which report that individuals with anorexia have a reduced appreciation of sweet tastes (81). In contrast, insulin is postulated to have an anorexigenic effect in the brain (82,83), partly through its inhibition of the orexigenic agouti-related peptide (AgRP) and neuropeptide Y (NPY) neurons (84,85). This may contradict the putative risk-decreasing effect of insulin on anorexia we observed in our study, however, there is evidence of a significant sexual dimorphism in this phenomenon.…”

Visceral adiposity and insular networks: associations with food craving

“…In this sense, a plausible interpretation could be that, at higher levels of visceral adiposity, there may be a need to increase the connectivity strength within mIns-frontoparietal network to drive homeostatic behavior in the face of reduced homeostatic information -linked to the reduced connectivity within the mIns-HYP/BNST network. Interestingly, in a recent report it has been shown that functional connectivity between homeostatic and cognitive centers of the brain could be modulated by insulin sensitivity (39). Future research may attempt to investigate how hormonal factors interact with the relationship between visceral adiposity and brain connectivity measurements.…”

Brain insulin sensitivity is linked to adiposity and body fat distribution

“…Recent imaging studies characterized a limited number of cortical and sub-cortical brain regions that respond to the peptide hormone, including the hypothalamus 6 . Insulin also impacts the functional inter-connection of these areas 7 , which underlines its importance in the control of larger networks within the brain.…”