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.
Highlights
Interactions between the central and peripheral nervous system influence various metabolic and cognitive functions[1, 2]
Group-averaged default-mode network (DMN) of lean and overweight/obese participants under baseline condition for the anterior medial prefrontal cortex (PFC) seed region is displayed in red
Bright green color-coded region reveals voxels within the hypothalamus showing a significant change in functional connectivity with the anterior medial PFC of the DMN, as identified by a significant interaction between condition and the peripheral insulin sensitivity index
Summary
Interactions between the central and peripheral nervous system influence various metabolic and cognitive functions[1, 2] In this process, numerous hormonal signals play an important role to exert their effects on eating behavior and body weight[2]. A recent study has shown that the central hubs of the DMN, the posterior cingulate cortex and medial prefrontal cortex, are functionally closely connected to the hypothalamus[40, 41]. It is currently not clear whether it is possible to boost functional connectivity of the DMN in young overweight and obese brain insulin resistant individuals to improve their eating behavior and metabolism. We acquired resting-state functional magnetic resonance imaging (fMRI) to measure functional connectivity of the brain in response to intranasal insulin and placebo administration
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