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Journal of Lipid Research, Vol. 45, 657-666, April 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

ASP enhances in situ lipoprotein lipase activity by increasing fatty acid trapping in adipocytes

May Faraj, Allan D. Sniderman and Katherine Cianflone¹

Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Center, Montréal, Canada

¹ To whom correspondence should be addressed. e-mail: katherine.cianflone{at}mcgill.ca

Acylation-stimulating protein (ASP) increases triglyceride (TG) storage (fatty acid trapping) in adipose tissue and plays an important role in postprandial TG clearance. We examined the capacity of ASP and insulin to stimulate the activity of lipoprotein lipase (LPL) and the trapping of LPL-derived nonesterified fatty acid (NEFA) in 3T3-L1 adipocytes. Although insulin increased total LPL activity (secreted and cell-associated; P < 0.001) in 3T3-L1 adipocytes, ASP moderately stimulated secreted LPL activity (P = 0.04; 5% of total LPL activity). Neither hormone increased LPL translocation from adipocytes to endothelial cells in a coculture system. However, ASP and insulin increased the V_max of in situ LPL activity ([³H]TG synthetic lipoprotein hydrolysis and [³H]NEFA incorporation into adipocytes) by 60% and 41%, respectively (P 0.01) without affecting K_m. Tetrahydrolipstatin (LPL inhibitor) diminished baseline, ASP-, and insulin-stimulated in situ LPL activity, resulting in [³H]TG accumulation (P < 0.0001). Unbound oleate inhibited in situ LPL activity (P < 0.0001) but did not eliminate the ASP stimulatory effect.

Therefore, 1) the clearance of TG-rich lipoproteins is enhanced by ASP through increasing TG storage and relieving NEFA inhibition of LPL; and 2) the effectiveness of adipose tissue trapping of LPL-derived NEFAs determines overall LPL activity, which in turn determines the efficiency of postprandial TG clearance.

Abbreviations: ASP, acylation-stimulating protein; CPAE, calf pulmonary artery endothelial; DG, diglyceride; LPL, lipoprotein lipase; NEFA, nonesterified fatty acid; TG, triglyceride; THL, tetrahydrolipstatin

Supplementary key words C3adesArg • insulin • triglyceride • acylation-stimulating protein

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