Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.
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.


RESULTS
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.


CONCLUSIONS
Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.
Lång
Pernilla
P
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
van Harmelen
Vanessa
V
Rydén
Mikael
M
Kaaman
Maria
M
Parini
Paolo
P
Carneheim
Claes
C
Cassady
A Ian
AI
Hume
David A
DA
Andersson
Göran
G
Arner
Peter
P
D000135:Acid Phosphatase / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000201:enzymology; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight; D017931:DNA Primers; D019281:Dimerization; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007333:Insulin Resistance / Q000235:genetics*; D007527:Isoenzymes / Q000378:metabolism*; D050155:Lipogenesis; D008066:Lipolysis; D008264:Macrophages / Q000166:cytology / Q000201:enzymology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000201:enzymology; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071681:Tartrate-Resistant Acid Phosphatase
D015415:Biomarkers; D017931:DNA Primers; D007527:Isoenzymes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase