Amyloid Precursor Protein Expression Is Upregulated in Adipocytes in Obesity

Diabetes and Metabolism Translational Medicine Unit, University of Vermont College of Medicine, Burlington, Vermont, USA.
Obesity (Impact Factor: 3.73). 08/2008; 16(7):1493-500. DOI: 10.1038/oby.2008.267
Source: PubMed


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.

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    • " - obese Pima Indians prior to GSEA software development found that inflammation / immune response genes were highly represented in the population of genes up - regulated in obesity , but did not identify any inflammasome - related genes . ( Lee et al . , 2005 ) Two later microarray studies found increased expression of amyloid precursor protein ( Lee et al . , 2008 ) and inhibin B ( Sjoholm et al . , 2006 ) in adipocytes of obese vs . lean subjects , but did not perform gene pathway analyses . NLRP3 expression and inflammasome activation are triggered by hyperglycemia , saturated FFAs , ceramide , reactive oxygen spe - cies and urate , calcium and cholesterol crystals ( Latz , 2010 ; Vandanmagsar "
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    • "Recent studies have implicated adipose tissue in the generation of Aβ, finding that APP, the parent protein of Aβ, is highly expressed in adipose tissue, and that adipose APP expression is upregulated in obese individuals [32]. Further, plasma Aβ levels correlate with adipocyte APP expression in obese individuals [33]. "
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    • "Elevation of plasma Aβ might be a partial result from obesity, because it has been reported that APP expression is upregulated in subcutaneous abdominal adipocytes from obese subjects (42) and that the plasma Aβ level is positively correlated with body fat in healthy individuals (43). Elevation of plasma Aβ also might be a consequence of increased age, because plasma Aβ40/42 levels have been reported to increase with age in humans (41). "
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