Abstract
BackgroundInsulin is an anorexigenic hormone that contributes to the termination of food intake in the postprandial state. An alteration in insulin action in the brain, named “cerebral insulin resistance”, is responsible for overeating and the development of obesity.Methodology/Principal FindingsTo analyze the direct effect of insulin on food-related neuronal activity we tested 10 lean and 10 obese subjects. We conducted a magnetencephalography study during a visual working memory task in both the basal state and after applying insulin or placebo spray intranasally to bypass the blood brain barrier. Food and non-food pictures were presented and subjects had to determine whether or not two consecutive pictures belonged to the same category.Intranasal insulin displayed no effect on blood glucose, insulin or C-peptide concentrations in the periphery; however, it led to an increase in the components of evoked fields related to identification and categorization of pictures (at around 170 ms post stimuli in the visual ventral stream) in lean subjects when food pictures were presented. In contrast, insulin did not modulate food-related brain activity in obese subjects.Conclusions/SignificanceWe demonstrated that intranasal insulin increases the cerebral processing of food pictures in lean whereas this was absent in obese subjects. This study further substantiates the presence of a “cerebral insulin resistance” in obese subjects and might be relevant in the pathogenesis of obesity.
Highlights
Obesity with its growing incidence and prevalence and its costs for the health system is currently a research focus in different scientific disciplines ranging from internal medicine to neuroscience
Conclusions/Significance: We demonstrated that intranasal insulin increases the cerebral processing of food pictures in lean whereas this was absent in obese subjects
Previous studies suggested that the increase in cortical activity during a hyperinsulinemic-euglycemic clamp is prominent in lean subjects whereas this effect was suppressed in obese subjects [14] which indicates insulin resistance in the brain
Summary
Obesity with its growing incidence and prevalence and its costs for the health system is currently a research focus in different scientific disciplines ranging from internal medicine to neuroscience. In the present study, insulin was administered intranasally to enter the brain via the olfactory nerve and bulb and to raise insulin concentrations in the cerebrospinal fluid without relevant absorption to the systemic blood circulation [19,20,21]. In this respect, intranasal insulin is a useful tool to determine the effect of insulin in the brain without affecting glucose metabolism in the periphery. In our previous study with MEG [24] we were able to show the temporal sequence of neuronal activation during visual processing of food pictures, whereas in the current study we have focused on the effect of insulin in this network
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