The hypolipidemic action of bezafibrate therapy in hypertriglyceridemia is mediated by upregulation of lipoprotein lipase: no effects on VLDL substrate affinity to lipolysis or LDL receptor binding.
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de Man FH, de Beer F, van der Laarse A, Jansen H, Leuven JA, Souverijn JH, Vroom TF, Schoormans SC, Fruchart JC, Havekes LM, Smelt AH
The hypolipidemic action of bezafibrate therapy in hypertriglyceridemia is mediated by upregulation of lipoprotein lipase: no effects on VLDL substrate affinity to lipolysis or LDL receptor binding.
Atherosclerosis. 2000 Dec;153(2):363-71.
- PubMed ID
- 11164425 [ View in PubMed]
- Abstract
Fibrates are regarded as drugs of choice in hypertriglyceridemia (HTG). Downregulation of apolipoprotein (apo) C-III gene expression and upregulation of lipoprotein lipase (LPL) gene expression have been suggested to explain the hypolipidemic action of fibrates. This study was designed to study the effects of bezafibrate therapy on very low density lipoprotein (VLDL) susceptibility to lipolysis, VLDL binding to the low density lipoprotein (LDL) receptor and postheparin LPL activities in patients with HTG. VLDL lipolysis was studied with heparan sulfate proteoglycan-bound LPL. Binding affinity of VLDL to the LDL receptor was determined in J774 cells with 125I-labeled control LDL. Eighteen HTG patients were randomized to receive, in a double-blind placebo-controlled cross-over fashion, 400 mg bezafibrate once daily for 6 weeks. In response to bezafibrate therapy, plasma triglyceride and apoC-III levels decreased by 69 and 42%, respectively. HTG VLDL was lipolyzed less efficiently compared to control VLDL, and lipolysis did not improve by bezafibrate therapy. VLDL binding affinity to the LDL receptor was comparable between the control group and HTG group, and did not change upon bezafibrate therapy. However, the post-heparin LPL activity in the HTG patients increased from 153 to 192 U/l (P = 0.025). A strong inverse relation was observed between the change in LPL activities and the change in triglyceride levels (r = -0.62, P = 0.006). In conclusion, the hypolipidemic action of bezafibrate therapy in HTG may be attributed to increased LPL activity, whereas VLDL susceptibility to lipolysis and LDL receptor binding are not affected.
DrugBank Data that Cites this Article
- Pharmaco-metabolomics
Drug Drug Groups Metabolite Change Description Bezafibrate Approved Investigational Triglycerides decreased Bezafibrate decreases the level of Triglycerides in the blood - Pharmaco-proteomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Bezafibrate Approved Investigational APOC3 345 decreased Bezafibrate results in decreased expression of APOC3 protein 11q23.3