Tissue alkaline phosphatase is involved in lipid metabolism and gene expression and secretion of adipokines in adipocytes

Background: Alkaline phosphatases are dimeric hydrolytic Enzymes that dephosphorylate nucleotides and proteins. AP-TNAP is found primarily in skeletal tissues were it plays a major role in the mineralization of the extracellular matrix and bone formation.

Methods: In this study we found through conventional and real time PCR assays that Alpl, the gene encoding for AP-TNAP is expressed in adipose tissue and in 3 T3-F442A adipocytes. We evaluated, using RNAi its role in adipocyte metabolism, and its cytoplasmic location by immunohistochemistry.

Results: Alpl is highly expressed late in adipogenesis during adipose terminal differentiation. Knocking down Alpl increased the expression of the genes encoding for glycerophosphate dehydrogenase, and for the adipokines Adiponectin, and FABP4 (aP2) but decreased that of Leptin, and it also increased secretion of FABP4; these 3 proteins are important in adipocyte systemic signaling and Insulin sensitivity. Inhibition of Alkaline Phosphatase activity in adipocytes by levamisole reduced lipolysis and the expression of various lipogenic genes. We found the Enzyme intracytoplasmically, forming aggregates in close surroundings of the lipid droplets during lipolysis.

Conclusions: We suggest that AP-TNAP activity is involved in lipid and energy metabolism of fat cells, and it might regulate glucose metabolism and Insulin sensitivity via adipokine synthesis and secretion.

General significance: The activity of AP-TNAP might have a critical role in the energy balance of the adipocyte, probably participating in obesity and metabolic syndrome.

3 T3-F442A adipocytes; AP-TNAP; Adipogenesis; Alkaline phosphatase.