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Inhibitors of hepatic microsomal triacylglycerol hydrolase decrease very low density lipoprotein secretion
Author(s) -
Gilham Dean,
Ho Samuel,
Rasouli Mehdi,
Martres Paul,
Vance Dennis E.,
Lehner Richard
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0728fje
Subject(s) - apolipoprotein b , very low density lipoprotein , secretion , lipoprotein lipase , microsomal triglyceride transfer protein , endocrinology , chemistry , medicine , lipolysis , hepatic lipase , lipoprotein , cholesteryl ester , monoacylglycerol lipase , lipid droplet , biochemistry , enzyme , biology , cholesterol , adipose tissue , receptor , endocannabinoid system
The presence of elevated circulating triacylglycerol (TG)‐rich very low density lipoprotein (VLDL) and apolipoprotein B‐100 (apoB‐100) levels represents an independent risk factor for coronary artery disease. Triacylglycerol hydrolase catalyzes the mobilization of cytoplasmic TG stores. To test the hypothesis that the enzyme plays a role in the provision of core lipids for the assembly of VLDL, we inhibited the lipase activity in primary rat hepatocytes and analyzed lipid and apoB synthesis and secretion. Inhibition of lipolysis resulted in a dramatic decrease in secretion of TGs. In addition, secretion of cholesteryl ester and phosphatidylcholine was substantially decreased. Analysis of secreted apolipoproteins indicated that apoB‐100 secretion was much more sensitive to lipase inhibition than was apoB‐48 secretion, perhaps because of the ability of apoB‐48 to be secreted as a relatively lipid‐poor particle. The results agreed with those obtained with hepatoma cells transfected with triacylglycerol hydrolase cDNA, in which preferential lipidation of apoB‐100 was observed. Together, our findings provide evidence that inhibition of intracellular TG hydrolysis significantly decreases apoB‐100 secretion and suggest that triacylglycerol hydrolase may be a suitable pharmacological target in efforts to lower plasma lipid levels.