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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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          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 references 9

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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.

                Author and article information

                S. Karger AG
                March 1999
                19 March 1999
                : 69
                : 3
                : 154-159
                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
                54414 Neuroendocrinology 1999;69:154–159
                © 1999 S. Karger AG, Basel

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


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