Table 3.
Mechanisms implicated in the lipid-modifying activity of niacin, fibrates and omega-3 fatty acids
| Drug | Proposed mechanisms |
|---|---|
| Niacin156,158–161,166 | Not clear. the following have been implicated: |
| ↓ TG synthesis and hepatic secretion of VLDL | |
| Possibly, direct inhibition of DGAT-2 | |
| Partial inhibition of hormone sensitive TG lipase in adipose tissue | |
| Up-regulation of apo A-I production | |
| Possibly, delayed catabolism of larger HDL particles | |
| Potential attenuation of CETP activity | |
| Fibrate156,162–166 | Transcriptional regulation mediated via interaction with PPARα. Pathways involved include: |
| ↑ catabolism of VLDL, IDL, and LDL apo B100 due to ↑ LPL expression and activity | |
| ↓ production rate of apo CIII, thereby potentiating LPL activity (fenofibrate) | |
| ↑ VLDL apo B or VLDL-TG turnover (bezafibrate, gemfibrozil) | |
| ↑ production of apo A-II and lipoprotein AI:AII although no change in lipoprotein A-I with fenofibrate | |
| ↑ HDL2a/HDL3a,linked to reduced CETP activity | |
| Omega-3 fatty acids138,157,167–170 | Transcriptional regulation of SREBP-1c and PPARα |
| Inhibition of hormone-sensitive TG lipase and stimulation of LPL possibly through regulation of PPARδ | |
| ↓ TG secretion and and lipogenesis | |
| ↑ mitochondrial and peroxisomal fatty acid oxidation | |
| Inhibition of DGAT-2 | |
| ↓ VLDL B secretion, specifically VLDL1 | |
| ↑ conversion of VLDL to LDL | |
| ↓ catabolism of HDL apo A-I | |
apo, apolipoprotein; CETP, cholesteryl ester transfer protein; DGAT-2, diacylglycerol O-acyltransferase 2; IDL, intermediate-density lipoproteins; LPL, lipoprotein lipase; PPAR, peroxisome proliferator-activated receptor; SREBP, sterol regulatory element binding proteins; TG, triglycerides; VLDL, very low-density lipoproteins.