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      The Insulin-Mediated Modulation of Visually Evoked Magnetic Fields Is Reduced in Obese Subjects

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          Abstract

          Background

          Insulin 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 Findings

          To 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/Significance

          We 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.

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          Most cited references38

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          Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons.

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            Low dopamine striatal D2 receptors are associated with prefrontal metabolism in obese subjects: possible contributing factors.

            Dopamine's role in inhibitory control is well recognized and its disruption may contribute to behavioral disorders of discontrol such as obesity. However, the mechanism by which impaired dopamine neurotransmission interferes with inhibitory control is poorly understood. We had previously documented a reduction in dopamine D2 receptors in morbidly obese subjects. To assess if the reductions in dopamine D2 receptors were associated with activity in prefrontal brain regions implicated in inhibitory control we assessed the relationship between dopamine D2 receptor availability in striatum with brain glucose metabolism (marker of brain function) in ten morbidly obese subjects (BMI>40 kg/m(2)) and compared it to that in twelve non-obese controls. PET was used with [(11)C]raclopride to assess D2 receptors and with [(18)F]FDG to assess regional brain glucose metabolism. In obese subjects striatal D2 receptor availability was lower than controls and was positively correlated with metabolism in dorsolateral prefrontal, medial orbitofrontal, anterior cingulate gyrus and somatosensory cortices. In controls correlations with prefrontal metabolism were not significant but comparisons with those in obese subjects were not significant, which does not permit to ascribe the associations as unique to obesity. The associations between striatal D2 receptors and prefrontal metabolism in obese subjects suggest that decreases in striatal D2 receptors could contribute to overeating via their modulation of striatal prefrontal pathways, which participate in inhibitory control and salience attribution. The association between striatal D2 receptors and metabolism in somatosensory cortices (regions that process palatability) could underlie one of the mechanisms through which dopamine regulates the reinforcing properties of food.
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              Transport of drugs from the nasal cavity to the central nervous system.

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                11 May 2011
                : 6
                : 5
                : e19482
                Affiliations
                [1 ]Internal Medicine IV, Department of Endocrinology and Diabetes, Angiology, Nephrology and Clinical Chemistry, University Hospital, University of Tübingen, Tübingen, Germany
                [2 ]MEG Center, University of Tübingen, Tübingen, Germany
                [3 ]Center for Ophthalmology, University of Tübingen, Tübingen, Germany
                [4 ]Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany
                [5 ]Department for Obstetrics and Gynecology, Medical College, University of Arkansas, Little Rock, Arkansas, United States of America
                University of Las Palmas de Gran Canaria, Spain
                Author notes

                Conceived and designed the experiments: MG KTS OT KS MR H-UH AF HP. Performed the experiments: MG KTS MR MHeni. Analyzed the data: MG KTS HP AMH. Contributed reagents/materials/analysis tools: MHallschmid. Wrote the paper: MG KTS MHallschmid H-UH AF HP AMH.

                Article
                PONE-D-10-00977
                10.1371/journal.pone.0019482
                3092755
                21589921
                03cbc53a-b53b-4238-acd8-1919c7f0cf10
                Guthoff et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 19 August 2010
                : 8 April 2011
                Page count
                Pages: 7
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Endocrine System
                Endocrine Physiology
                Neuroendocrinology
                Biochemistry
                Neurochemistry
                Neuroendocrinology
                Neuroscience
                Behavioral Neuroscience
                Neuroimaging
                Medicine
                Endocrinology
                Diabetic Endocrinology
                Diabetes Mellitus Type 2
                Insulin
                Metabolic Disorders
                Neurology
                Neuroimaging
                Nutrition
                Obesity

                Uncategorized
                Uncategorized

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