title: Analysis of White Adipose Tissue Gene Expression Reveals CREB1 Pathway Altered in Huntington's Disease.
abstract: BACKGROUND
  In addition to classical neurological symptoms, Huntington's disease (HD) is complicated by peripheral pathology and both the mutant gene and the protein are found in cells and tissues throughout the body. Despite the adipose tissue gene expression alterations described in HD mouse models, adipose tissue and its gene expression signature have not been previously explored in human HD.
  
  
  OBJECTIVE
  We investigated gene expression signatures in subcutaneous adipose tissue obtained from control subjects, premanifest HD gene carriers and manifest HD subjects with the aim to identify gene expression changes and signalling pathway alterations in adipose tissue relevant to HD.
  
  
  METHODS
  Gene expression was assessed using Affymetrix GeneChip® Human Gene 1.0 ST Array. Target genes were technically validated using real-time quantitative PCR and the expression signature was validated in an independent subject cohort.
  
  
  RESULTS
  In subcutaneous adipose tissue, more than 500 genes were significantly different in premanifest HD subjects as compared to healthy controls. Pathway analysis suggests that the differentially expressed genes found here in HD adipose tissue are involved in fatty acid metabolism pathways, angiotensin signalling pathways and immune pathways. Transcription factor analysis highlights CREB1. Using RT-qPCR, we found that MAL2, AGTR2, COBL and the transcription factor CREB1 were significantly upregulated, with CREB1 and AGT also being significantly upregulated in a separate cohort.
  
  
  CONCLUSIONS
  Distinct gene expression profiles can be seen in HD subcutaneous adipose tissue, with CREB1 highlighted as a key transcription factor.
authors.affiliation: Brain Disease Biomarker unit, Department of Experimental Medical Science, Wallenberg Neuroscience Centre, Lund University, Lund, Sweden.
authors.forename: Andrew Christopher
authors.initials: AC
authors.lastname: McCourt
authors.affiliation: Institute of Neurology, Department of Neurodegenerative Disease, UCL, London, UK.|Magnus Life Science, Rayne Building, 5 University Street, London, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Parker
authors.affiliation: Brain Disease Biomarker unit, Department of Experimental Medical Science, Wallenberg Neuroscience Centre, Lund University, Lund, Sweden.|Faculty of Life Sciences, Michael Smith Building, Oxford Road, Manchester, M13 9PT, UK.
authors.forename: Edina
authors.initials: E
authors.lastname: Silajdžić
authors.affiliation: Institute of Neurology, Department of Neurodegenerative Disease, UCL, London, UK.
authors.forename: Salman
authors.initials: S
authors.lastname: Haider
authors.affiliation: Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, London, UK.
authors.forename: Huma
authors.initials: H
authors.lastname: Sethi
authors.affiliation: Institute of Neurology, Department of Neurodegenerative Disease, UCL, London, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Tabrizi
authors.affiliation: Reta Lila Weston Institute, UCL Institute of Neurology, London, UK.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Warner
authors.affiliation: Brain Disease Biomarker unit, Department of Experimental Medical Science, Wallenberg Neuroscience Centre, Lund University, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Björkqvist
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism*; D000328:Adult; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C534931:AGT protein, human; C115163:CREB1 protein, human; D002352:Carrier Proteins; C561633:Cobl protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C438606:MAL2 protein, human; D008840:Microfilament Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D044139:Receptor, Angiotensin, Type 2; D014157:Transcription Factors; D000808:Angiotensinogen; C067133:corticotropin releasing factor-binding protein
keywords: CREB1; Huntington’s disease; adipose tissue; gene expression