The effect of alkaline phosphatase inhibitors on intracellular lipid accumulation in preadipocytes isolated from human mammary tissue.
BACKGROUND
A previous study has demonstrated that alkaline phosphatase (AP) may play a role in the control of intracellular lipid accumulation in the rodent preadipocyte cell line, 3T3-L1. The present study investigated whether AP may have a similar function in preadipocytes isolated from human mammary gland tissue.


METHODS
Preadipocyte maturation was induced in the presence or absence of the tissue non-specific AP inhibitors levamisole and histidine, and the tissue-specific AP inhibitor PheGlyGly. Cellular AP activity and adipogenesis were both assessed at 0 and 12 days post-induction of differentiation.


RESULTS
After differentiation, AP activity increased 5.1 +/- 1.3-fold in the absence and 8.9 +/- 2.8-fold (P < 0.05) in the presence of levamisole. However, adipogenesis increased 1.95 +/- 0.11-fold in the absence but only 1.36 +/- 0.06-fold (P < 0.001) in the presence of levamisole. There was a 4.2 +/- 2.2-fold increase in AP activity in the absence and a 0.51 +/- 0.46-fold (P < 0.05) decrease in the presence of histidine. Adipogenesis increased 2.09 +/- 0.35-fold in the absence of histidine but only 1.22 +/- 0.30-fold (P < 0.05) in the presence of histidine. PheGlyGly had no effects. Fluorescent microscopy showed AP activity was localized to the triglyceride-containing droplets of the cell.


CONCLUSIONS
This is the first study to show that tissue non-specific AP inhibitors can block adipogenesis in human preadipocytes.
Ali
Aus T
AT
Department of Chemical Pathology, National Health Laboratory Service, South Africa.
Penny
Clem B
CB
Paiker
Janice E
JE
Psaras
George
G
Ikram
Faisel
F
Crowther
Nigel J
NJ
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006639:Histidine / Q000494:pharmacology; D006801:Humans; D007978:Levamisole / Q000494:pharmacology; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis*; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology
D004791:Enzyme Inhibitors; D008055:Lipids; D009842:Oligopeptides; C043963:phenylalanyl-glycyl-glycine; D007978:Levamisole; D006639:Histidine; D000469:Alkaline Phosphatase