ASP enhances in situ lipoprotein lipase activity by increasing fatty acid trapping in adipocytes.
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 ([(3)H]TG synthetic lipoprotein hydrolysis and [(3)H]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 [(3)H]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.
Faraj
May
M
Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Center, Montréal, Canada.
Sniderman
Allan D
AD
Cianflone
Katherine
K
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002478:Cells, Cultured; D018920:Coculture Techniques; D015926:Complement C3a / Q000031:analogs & derivatives* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008071:Lipoprotein Lipase / Q000378:metabolism*; D051379:Mice; D011651:Pulmonary Artery / Q000166:cytology
D005227:Fatty Acids; D007328:Insulin; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a; D008071:Lipoprotein Lipase