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  • Monomeric Tartrate Resistant Acid Phosphatase Induces Insulin Sensitive Obesity

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    Author(s)
    Lang, Pernilla
    van Harmelen, Vanessa
    Ryden, Mikael
    Kaaman, Maria
    Parini, Paolo
    Carneheim, Claes
    Cassady, A Ian
    Hume, David A
    Andersson, Goran
    Arner, Peter
    Griffith University Author(s)
    Cassady, Ian
    Year published
    2008
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    Abstract
    Background: Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP) is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer. Principal Findings: Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic ...
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    Background: Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP) is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer. Principal Findings: Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity. Conclusion: Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.
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    Journal Title
    PloS One
    Volume
    3
    Issue
    3
    DOI
    https://doi.org/10.1371/journal.pone.0001713
    Copyright Statement
    © 2008 Lång et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)
    Subject
    Animal cell and molecular biology
    Medical biochemistry - proteins and peptides (incl. medical proteomics)
    Publication URI
    http://hdl.handle.net/10072/57243
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    • Journal articles

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