The effect of alkaline phosphatase inhibitors on intracellular lipid accumulation in preadipocytes isolated from human mammary tissue

Abstract

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. Conclusion: This is the first study to show that tissue non-specific AP inhibitors can block adipogenesis in human preadipocytes.