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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
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نویسنده
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olszewski p.k. ,rozman j. ,jacobsson j.a. ,rathkolb b. ,strömberg s. ,hans w. ,klockars a. ,alsiö j. ,risérus u. ,becker l. ,hölter s.m. ,elvert r. ,ehrhardt n. ,gailus-durner v. ,fuchs h. ,fredriksson r. ,wolf e. ,klopstock t. ,wurst w. ,levine a.s. ,marcus c. ,de angelis m.h. ,klingenspor m. ,schiöth h.b. ,kilimann m.w.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 3
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چکیده
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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. © 2012 olszewski et al.
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آدرس
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functional pharmacology unit,department of neuroscience,uppsala university,uppsala,sweden,minnesota obesity center,university of minnesot,st. paul,mn,united states,department of biological sciences,university of waikato,hamilton, New Zealand, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,germany,molecular nutritional medicine,else kröner-fresenius center and ziel research center for nutrition and food sciences,technische universität münchen,freising-weihenstephan, Germany, functional pharmacology unit,department of neuroscience,uppsala university,uppsala, Sweden, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,germany,chair for molecular animal breeding and biotechnology,gene center,ludwig-maximilians-universität münchen,münchen, Germany, molecular cell biology unit,department of neuroscience,uppsala university,uppsala, Sweden, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, functional pharmacology unit,department of neuroscience,uppsala university,uppsala, Sweden, functional pharmacology unit,department of neuroscience,uppsala university,uppsala, Sweden, department of public health and caring sciences,uppsala university,uppsala, Sweden, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,germany,department of neurology,friedrich-baur-institut,ludwig-maximilians-universität münchen,münchen, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,germany,helmholtz zentrum münchen,german research center for environmental health,institute of developmental genetics,neuherberg, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,germany,sanofi-aventis gmbh,frankfurt am main, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,germany,department of medical genetics,cedars-sinai medical center,los angeles,ca, United States, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg, Germany, functional pharmacology unit,department of neuroscience,uppsala university,uppsala, Sweden, chair for molecular animal breeding and biotechnology,gene center,ludwig-maximilians-universität münchen,münchen, Germany, department of neurology,friedrich-baur-institut,ludwig-maximilians-universität münchen,münchen, Germany, helmholtz zentrum münchen,german research center for environmental health,institute of developmental genetics,neuherberg,germany,max-planck-institute for psychiatry,münchen,germany,technical university münchen-weihenstephan,lehrstuhl fur entwicklungsgenetik c/o helmholtz,neuherberg,germany,deutsches zentrum für neurodegenerative erkrankungen (dzne) munich, Germany, minnesota obesity center,university of minnesot,st. paul,mn, United States, department for clinical science,intervention,and technology,karolinska institutet,division of pediatrics,national childhood obesity centre,stockholm, Sweden, german mouse clinic,institute of experimental genetics,helmholtz zentrum münchen,german research center for environmental health,neuherberg,germany,lehrstuhl für experimentelle genetik,technische universität münchen,freising-weihenstephan, Germany, molecular nutritional medicine,else kröner-fresenius center and ziel research center for nutrition and food sciences,technische universität münchen,freising-weihenstephan, Germany, functional pharmacology unit,department of neuroscience,uppsala university,uppsala, Sweden, molecular cell biology unit,department of neuroscience,uppsala university,uppsala, Sweden
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Authors
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