title: Amyloid precursor protein expression is upregulated in adipocytes in obesity.
abstract: The aim of this study was to determine whether amyloid precursor protein (APP) is expressed in human adipose tissue, dysregulated in obesity, and related to insulin resistance and inflammation. APP expression was examined by microarray expression profiling of subcutaneous abdominal adipocytes (SAC) and cultured preadipocytes from obese and nonobese subjects. Quantitative real-time PCR (QPCR) was performed to confirm differences in APP expression in SAC and to compare APP expression levels in adipose tissue, adipocytes, and stromal vascular cells (SVCs) from subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) specimens. Adipose tissue samples were also examined by western blot and immunofluorescence confocal microscopy. Microarray studies demonstrated that APP mRNA expression levels were higher in SAC (approximately 2.5-fold) and preadipocytes (approximately 1.4) from obese subjects. Real-time PCR confirmed increased APP expression in SAC in a separate group of obese compared with nonobese subjects (P=0.02). APP expression correlated to in vivo indices of insulin resistance independently of BMI and with the expression of proinflammatory genes, such as monocyte chemoattractant protein-1 (MCP-1) (R=0.62, P=0.004), macrophage inflammatory protein-1alpha (MIP-1alpha) (R=0.60, P=0.005), and interleukin-6 (IL-6) (R=0.71, P=0.0005). Full-length APP protein was detected in adipocytes by western blotting and APP and its cleavage peptides, Abeta40 and Abeta42, were observed in SAT and VAT by immunofluorescence confocal microscopy. In summary, APP is highly expressed in adipose tissue, upregulated in obesity, and expression levels correlate with insulin resistance and adipocyte cytokine expression levels. These data suggest a possible role for APP and/or Abeta in the development of obesity-related insulin resistance and adipose tissue inflammation.
authors.affiliation: Diabetes and Metabolism Translational Medicine Unit, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: William G
authors.initials: WG
authors.lastname: Tharp
authors.forename: Rhonda L
authors.initials: RL
authors.lastname: Maple
authors.forename: Saraswathy
authors.initials: S
authors.lastname: Nair
authors.forename: Paska A
authors.initials: PA
authors.lastname: Permana
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pratley
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015992:Body Mass Index; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018613:Microscopy, Confocal; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D015434:Panniculitis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism; D016133:Polymerase Chain Reaction; D058255:Protease Nexins; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018836:Inflammation Mediators; D010446:Peptide Fragments; D058255:Protease Nexins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)