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      Serum Leptin and Regional Cerebral Blood Flow during Exposure to Food in Obese and Normal-Weight Women

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          Abstract

          Leptin is an adipocyte-derived product of the ob gene thought to be involved in the regulation of eating. Receptors for leptin have been found in multiple regions in the brain. In particular, hypothalamic receptors seem to be of fundamental importance for the biological effects of leptin. However, the association of leptin with cerebral function in humans has not been studied. Therefore, in order to assess the possible functional relationships between leptin and cerebral activity in humans, simultaneous serum leptin and regional cerebral blood flow (rCBF) measurements were made in 10 obese [BMI 33.5 (29.3–39.1) kg/m<sup>2</sup>] and 12 normal-weight [BMI 22.2 (20.3–24.6) kg/m<sup>2</sup>] women during exposure to food. The rCBF measurements were performed by <sup>99m</sup>Tc-ethyl-cysteine-dimer single photon emission computed tomography. A strong inverse association was observed between the leptin and rCBF of hypothalamus during the exposure to food in the obese (r = –0.73, p = 0.02, n = 10), but not in the normal-weight subjects (r = 0.22, p = 0.48, n = 12). This suggests that the association of leptin with cerebral activity could be different in obese and normal-weight women; depressed activity of hypothalamic neurones in response to the high peripheral leptin concentration could be postulated to occur in obese women during exposure to food.

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          Most cited references9

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          Abnormal splicing of the leptin receptor in diabetic mice.

          Mutations in the mouse diabetes (db) gene result in obesity and diabetes in a syndrome resembling morbid human obesity. Previous data suggest that the db gene encodes the receptor for the obese (ob) gene product, leptin. A leptin receptor was recently cloned from choroid plexus and shown to map to the same 6-cM interval on mouse chromosome 4 as db. This receptor maps to the same 300-kilobase interval as db, and has at least six alternatively spliced forms. One of these splice variants is expressed at a high level in the hypothalamus, and is abnormally spliced in C57BL/Ks db/db mice. The mutant protein is missing the cytoplasmic region, and is likely to be defective in signal transduction. This suggests that the weight-reducing effects of leptin may be mediated by signal transduction through a leptin receptor in the hypothalamus.
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            Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans.

            The adipocyte hormone, leptin (OB protein), is proposed to be an "adiposity signal" that acts in the brain to lower food intake and adiposity. As plasma leptin levels are elevated in most overweight individuals, obesity may be associated with leptin resistance. To investigate the mechanisms underlying brain leptin uptake and to determine whether reduced uptake may contribute to leptin resistance, we measured immunoreactive leptin levels in plasma and cerebrospinal fluid (CSF) of 53 human subjects. Leptin concentrations in CSF were strongly correlated to the plasma level in a nonlinear manner (r = 0.92; p = 0.0001). Like levels in plasma, CSF leptin levels were correlated to body mass index (r = 0.43; p = 0.001), demonstrating that plasma leptin enters human cerebrospinal fluid in proportion to body adiposity. However, the efficiency of this uptake (measured as the CSF:plasma leptin ratio) was lower among those in the highest as compared with the lowest plasma leptin quintile (5.4-fold difference). We hypothesize that a saturable mechanism mediates CSF leptin transport, and that reduced efficiency of brain leptin delivery among obese individuals with high plasma leptin levels results in apparent leptin resistance.
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              Design and synthesis of multi-haem proteins.

              A water-soluble, 62-residue, di-alpha-helical peptide has been synthesized which accommodates two bis-histidyl haem groups. The peptide assembles into a four-helix dimer with 2-fold symmetry and four parallel haems that closely resemble native haems in their spectral and electrochemical properties, including haem-haem redox interaction. This protein is an essential intermediate in the synthesis of molecular 'maquettes', a novel class of simplified versions of the metalloproteins involved in redox catalysis and in energy conversion in respiratory and photosynthetic electron transfer.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                1999
                March 1999
                19 March 1999
                : 69
                : 3
                : 154-159
                Affiliations
                aDepartment of Clinical Nutrition, University of Kuopio and Kuopio University Hospital; bA.I. Virtanen Institute, University of Kuopio; cDepartment of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland
                Article
                54414 Neuroendocrinology 1999;69:154–159
                10.1159/000054414
                10087447
                407ce4ec-55b4-4666-a21d-0750df10449f
                © 1999 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 2, Tables: 2, References: 28, Pages: 6
                Categories
                Leptin and Neuroendocrine Correlates of Food Intake

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Leptin,Imaging,Clinical neuroendocrinology,Cerebral blood flow,Food intake behavior,Obesity

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