Abstract
We have previously shown that in normolipidemic healthy adults, plasma acylation stimulating protein (ASP) increases postprandially and is produced in vitro by cultured differentiated human adipocytes. The present studies were undertaken to examine the influence of specific plasma components on endogenous ASP production in cultured human adipocytes. The results demonstrate that neither glucose nor fatty acids (over a wide range of concentrations) had any substantial effect on ASP production. Insulin increased ASP production up to 2-fold (208% +/- 18%, P < 0.01). However, the most profound increase in ASP was generated by the addition of chylomicrons to the cell culture medium. Chylomicrons (CHYLO) obtained from postprandial plasma increased ASP production in a time- and concentration-dependent manner, producing up to a 150-fold increase in ASP at the highest concentration of CHYLO tested (500 microg triacylglycerol/mL medium (P < 0.001)). By contrast, very low (VLDL), high (HDL), and low density lipoproteins (LDI) had only marginal effects. The effects on ASP parallelled the changes in adipocyte C3 secretion (the precursor protein of ASP). As with ASP, glucose, oleate, insulin, and hepatic lipoproteins (VLDL, LDL, and HDL) had little or no effect on C3 secretion. In contrast, CHYLO had an even greater effect on C3 secretion than on ASP generation. Finally, the effects of CHYLO on generation of ASP and C3 were not dependent on lipolysis of CHYLO by lipoprotein lipase (LPL). These results are consistent with the changes in plasma ASP seen postprandially, and suggests a role of ASP as a positive feedback regulator of triacylglycerol synthesis in adipose tissue.
Highlights
We have previously shown that in normolipidemic healthy adults, plasma acylation stimulating protein (ASP) increases postprandially and is produced in vitro by cultured differentiated human adipocytes
We have previously demonstrated that ASP is produced by cultured human differentiated adipocytes and that its production increases proportional to differentiation of adipocytes [17, 18]
As fatty acids and glucose provide essential building blocks for triacylglycerols and ASP is very effective in stimulating both triacylglycerol synthesis and glucose transport in human adipocytes, we first examined the effects of these two substrates on ASP production by cultiired human differentiated adipocytes
Summary
We have previously shown that in normolipidemic healthy adults, plasma acylation stimulating protein (ASP) increases postprandially and is produced in vitro by cultured differentiated human adipocytes. The effects of CHYLO on generation of ASP and C3 were not dependent on lipolysis of CHYLO by lipoprotein lipase ( L P L ). Supplementarykey words triacylglycerol postprandial metabolism adipose tissue complement C3 adenylate cyclase, increasing the production of CAMP which activates protein kinase A. This enzyme, in turn, phosphorylates hormone-sensitive lipase, activating it. Insulin does have a profound effect on glucose transport and on inhibition of lipolysis mediated by hormone-sensitive lipase, but has little effect on the fatty acid esterification process itself which produces triacylglycerol [5]. In addition to lipoprotein lipase (LPL), adipocytes are a source of cholesteryl ester transfer pro-
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