The biological significance of lipoprotein lipase modulation by phenobarbital and heparin.
When confluent cultures of 3T3 F442A cells were treated with insulin, differentiation occurred within 6 days as indicated by LPL secretion followed by increased intracellular levels of protein and triacylglycerol. PB increased LPL secretion 2- to 3-fold and intracellular LPL 3- to 10-fold in a time-dependent manner; these increments were less in proportion to the length of the time interval between confluence and initiation of PB treatment. These results are consistent with the notion that PB promotes conversion of adipocyte precursors to mature adipocytes by increasing the proportion of the former that become susceptible to the differentiating stimulus. Human subjects treated with heparin by continuous i.v. infusion over 4 days showed an initial decrease in serum triacylglycerol concentration in response to the initial bolus injection, accompanied by sharp increases in circulating LPL and HTGL, but the triacylglycerol concentration returned to normal within 24 hr. Rats infused with heparin by means of peritoneal implantation of osmotic minipumps demonstrated dose-dependent increases in circulating LPL, accompanied by reduction in heart muscle LPL but inconsistent changes in other tissues examined. Heparin had no effect on the clearance of circulating LPL but did reduce the total body pool of endothelial-bound enzyme. No changes in fasting triacylglycerol and free glycerol were observed, but exogenous VLDL were cleared at a faster rate in heparinized animals. Since the latter also manifested a decrease in de novo fatty acid synthesis, it seems that the heparinized rat is able to maintain circulating levels of triacylglycerol by efficient re-esterification of preformed fatty acids despite the enhanced lipolysis consequent upon higher plasma LPL activity.
Goldberg
D M
DM
Department of Clinical Biochemistry, University of Toronto, Canada.
Parkes
J G
JG
Chajek-Shaul
T
T
Bglibter
N
N
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005260:Female; D006493:Heparin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D010634:Phenobarbital / Q000494:pharmacology*; D011655:Pulmonary Embolism / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy / Q000201:enzymology; D014280:Triglycerides / Q000097:blood* / Q000378:metabolism
D008079:Lipoproteins, VLDL; D014280:Triglycerides; D006493:Heparin; D008071:Lipoprotein Lipase; D010634:Phenobarbital