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Arcuate Nucleus Transcriptome Profiling Identifies Ankyrin Repeat and Suppressor of Cytokine Signalling Box-Containing Protein 4 as a Gene Regulated by Fasting in Central Nervous System Feeding Circuits
dc.contributor.authorLi, J.-Y.en_US
dc.contributor.authorKuick, Rorken_US
dc.contributor.authorThompson, Robert C.en_US
dc.contributor.authorMisek, David E.en_US
dc.contributor.authorLai, Y. -M.en_US
dc.contributor.authorLiu, Y. -Q.en_US
dc.contributor.authorChai, B. -X.en_US
dc.contributor.authorHanash, Samir M.en_US
dc.contributor.authorGantz, Iraen_US
dc.date.accessioned2010-06-01T20:22:29Z
dc.date.available2010-06-01T20:22:29Z
dc.date.issued2005-06en_US
dc.identifier.citationLi, J.-Y.; Kuick, R.; Thompson, R. C.; Misek, D. E.; Lai, Y.-M.; Liu, Y.-Q.; Chai, B.-X.; Hanash, S. M.; Gantz, I. (2005). "Arcuate Nucleus Transcriptome Profiling Identifies Ankyrin Repeat and Suppressor of Cytokine Signalling Box-Containing Protein 4 as a Gene Regulated by Fasting in Central Nervous System Feeding Circuits." Journal of Neuroendocrinology 17(6): 394-404. <http://hdl.handle.net/2027.42/73490>en_US
dc.identifier.issn0953-8194en_US
dc.identifier.issn1365-2826en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/73490
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=15929745&dopt=citationen_US
dc.description.abstractThe arcuate nucleus of the hypothalamus is a primary site for sensing blood borne nutrients and hormonal messengers that reflect caloric status. To identify novel energy homeostatic genes, we examined RNA extracts from the microdissected arcuate nucleus of fed and 48-h fasted rats using oligonucleotide microarrays. The relative abundance of 118 mRNA transcripts was increased and 203 mRNA transcripts was decreased during fasting. One of the down-regulated mRNAs was ankyrin-repeat and suppressor of cytokine signalling box-containing protein 4 (Asb-4). The predicted structure of Asb-4 protein suggested that it might encode an intracellular regulatory protein, and therefore its mRNA expression was investigated further. Reverse transcription quantitative polymerase chain reaction was used to validate down-regulation of Asb-4 mRNA in the arcuate nucleus of the fasted Sprague-Dawley rat (relative expression of Asb-4 mRNA: fed = 4.66 ± 0.26; fasted = 3.96 ± 0.23; n = 4, P < 0.01). Down-regulation was also demonstrated in the obese fa/fa Zucker rat, another model of energy disequilibrium (relative expression of Asb-4 mRNA: lean Zucker = 3.91 ± 0.32; fa/fa  = 2.93 ± 0.26; n = 5, P < 0.001). In situ hybridisation shows that Asb-4 mRNA is expressed in brain areas linked to energy homeostasis, including the arcuate nucleus, paraventricular nucleus, dorsomedial nucleus, lateral hypothalamus and posterodorsal medial amygdaloid area. Double in situ hybridisation revealed that Asb-4 mRNA colocalises with key energy homeostatic neurones. In the fed state, Asb-4 mRNA is expressed by 95.6% of pro-opiomelanocortin (POMC) neurones and 46.4% of neuropeptide Y (NPY) neurones. By contrast, in the fasted state, the percentage of POMC neurones expressing Asb-4 mRNA drops to 73.2% (P  <  0.001). Moreover, the density of Asb-4 mRNA per fasted POMC neurone is markedly decreased. Conversely, expression of Asb-4 mRNA by NPY neurones in the fasted state is modestly increased to 52.7% (P  <  0.05). Based on its differential expression, neuroanatomical distribution and colocalisation, we hypothesise that Asb-4 is a gene involved in energy homeostasis.en_US
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dc.format.extent3109 bytes
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dc.publisherBlackwell Science Ltden_US
dc.rights2005 Blackwell Publishing Ltden_US
dc.subject.otherObesityen_US
dc.subject.otherPro-opiomelanocortinen_US
dc.subject.otherNeuropeptide Yen_US
dc.subject.otherHypothalamusen_US
dc.subject.otherPosterior Hypothalamusen_US
dc.subject.otherAmygdalaen_US
dc.titleArcuate Nucleus Transcriptome Profiling Identifies Ankyrin Repeat and Suppressor of Cytokine Signalling Box-Containing Protein 4 as a Gene Regulated by Fasting in Central Nervous System Feeding Circuitsen_US
dc.typeArticleen_US
dc.subject.hlbsecondlevelNeurosciencesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationum§ Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.en_US
dc.contributor.affiliationother* Surgeryen_US
dc.contributor.affiliationother† Pediatricsen_US
dc.contributor.affiliationother† Psychiatryen_US
dc.identifier.pmid15929745en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/73490/1/j.1365-2826.2005.01317.x.pdf
dc.identifier.doi10.1111/j.1365-2826.2005.01317.xen_US
dc.identifier.sourceJournal of Neuroendocrinologyen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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