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      Neurobeachin, a regulator of synaptic protein targeting, is associated with body fat mass and feeding behavior in mice and body-mass index in humans

      Olszewski, Pawel K.; Rozman, Jane; Jacobsson, Josefin A.; Rathkolb, Birgit; Stromberg, Siv; Hans, Wolfgang; Klockars, Anica; Alsiö, Johan; Riserus, Ulf; Becker, Lore; Holter, Sabine; Elvert, Ralf; Ehrhardt, Nicole; Gailus-Durner, Valérie; Fuchs, Helmut; Fredriksson, Robert; Wolf, Eckhard; Klopstock, Thomas; Wurst, Wolfgang; Levine, Allen S.; Marcus, Claude; de Angelis, Martin Hrabě; Klingenspor, Martin; Schiöth, Helgi B.; Kilimann, Manfred W.
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      DOI
       10.1371/journal.pgen.1002568
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      Olszewski, P. K., Rozman, J., Jacobsson, J. A., Rathkolb, B., Stromberg, S., Hans, W., … Kilimann, M. W. (2012). Neurobeachin, a regulator of synaptic protein targeting, is associated with body fat mass and feeding behavior in mice and body-mass index in humans. PLoS Genetics, 8(3), e1002568.
      Permanent Research Commons link: https://hdl.handle.net/10289/8888
      Abstract
      Neurobeachin (Nbea) regulates neuronal membrane protein trafficking and is required for the development and functioning of central and neuromuscular synapses. In homozygous knockout (KO) mice, Nbea deficiency causes perinatal death. Here, we report that heterozygous KO mice haploinsufficient for Nbea have higher body weight due to increased adipose tissue mass. In several feeding paradigms, heterozygous KO mice consumed more food than wild-type (WT) controls, and this consumption was primarily driven by calories rather than palatability. Expression analysis of feeding-related genes in the hypothalamus and brainstem with real-time PCR showed differential expression of a subset of neuropeptide or neuropeptide receptor mRNAs between WT and Nbea+/− mice in the sated state and in response to food deprivation, but not to feeding reward. In humans, we identified two intronic NBEA single-nucleotide polymorphisms (SNPs) that are significantly associated with body-mass index (BMI) in adult and juvenile cohorts. Overall, data obtained in mice and humans suggest that variation of Nbea abundance or activity critically affects body weight, presumably by influencing the activity of feeding-related neural circuits. Our study emphasizes the importance of neural mechanisms in body weight control and points out NBEA as a potential risk gene in human obesity.
      Date
      2012
      Type
      Journal Article
      Publisher
      Public Library of Science
      Rights
      © 2012 Olszewski 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.
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