Table 1.
Drugs used in dyslipidemia | Classical mechanism of action | Adipose tissue effects | Weight | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
AT mass/AT depots | Glucose metabolism/insulin sensitivity | Lipid metabolism | Adipokine expression | Antiatherogenic | Adipogenesis | Browning effect | Anti-inflammatory | ||||
↑ | ↓ | ||||||||||
Statins | ⊝ HMG -CoA reductase enzyme | ↓ EAT [63] | ⊝ caveolae dysfunction [89]; ⊝ GLUT4 expression and translocation [95]; NLRP3 inflammasome activation [195]; ⊕ ↑ SIRT1 and PGC-1α leading to PPARγ and GLUT4 [97–99]; modulation of adipokine expression [83, 97] |
⊕ lipolysis [62] ↓ lipid accumulation (⊕ LPL) [64, 65] ⊕ lipogenesis and ↑ lipid accumulation [196] |
Adiponectin [62, 67, 68, 73, 76, 80] | Leptin [67–71]; resistin [67, 72, 73]; IL-6 [67, 74–78]; PAI-1 [79–81]; MCP-1 [77, 78, 80, 82, 83]; visfatin [71] and TNFα [67, 68, 71, 77, 82, 83] | ⊕ PPARγ and SRBI expression (adipocyte uptake of oxLDL) [88, 90]; vide adipokine expression modulation |
⊝ [66, 101–103] ⊕ in vivo [107, 108] |
⊝ ER stress [82]; ⊕ iNOS expression [75, 85] |
— [98, 99] | |
Fibrates | PPARα agonists | ⊕ [115, 122] | ↓ [114, 117–120, 124, 125] | ||||||||
Bezafibrate | Nonselective | ⊕ FA oxidation [113–115] ⊝ lipogenesis [113] |
Adiponectin [130, 131] | TNFα [130, 131] | ⊕ UCP-1, 2, and 3 expression [113, 114] | ||||||
Gemfibrozil | Selective | ⊕ lipogenesis [116] | |||||||||
Fenofibrate | Selective | ↓ VAT [125] | ⊕ [119, 120, 125] | ⊕ FA oxidation [118, 119] ⊝ lipogenesis [121] |
Adiponectin [67, 126]; vaspin [124] | MCP1 [127]; TNFα [67, 125, 127, 128]; leptin [120, 125] | ⊕ oxLDL uptake [134] ⊕ CD36 expression [134] |
⊕ [117, 120] | ⊝ CD40 expression (AMPK pathway) [132] ⊝ AOX1 expression [133] |
↓ [117–120, 125] | |
Ezetimibe | ⊝ NPC1L1 transporter | ↓ VAT [155] | ⊕ [155] | Adiponectin [155] | Visfatin [156] | — [155] | |||||
Niacin | ⊝ HDL-apoA-I holoparticle receptor in hepatocytes | ⊝ [148, 151] | ⊕ lipolysis [144–146] ⊝ lipogenesis |
Adiponectin [145]; leptin (chronic treatment) [151] | MCP1, RANTES, fractalkine [150] | ↑ n-3 PUFAs and its metabolites [149]; ⊕ HDL-induced cholesterol efflux from adipocytes; ↑ HDL levels [140, 152] |
⊕ [154] | Vide adipokine effects |
⊕: stimulates; ⊝: inhibits; —: without effect; AT: adipose tissue; TG: triglycerides; HMG-CoA: 3-hydroxy-3-methyl-glutaryl-coenzyme A; GLUT4: glucose transporter type 4; NLRP3: NOD-like receptor family, pyrin domain containing 3; SIRT1: sirtuin 1; PPARs: peroxisome proliferator-activated receptors; PGC-1α: peroxisome proliferator-activated receptor γ coactivator 1 alpha; LPL: lipoprotein lipase; TNFα: tumour necrosis factor α; IL: interleukin; CCL2 or MCP-1: CC-chemokine ligand 2; PAI-1: plasminogen activator inhibitor type 1; SRB1: scavenger receptor 1; oxLDL: oxidized LDL; CD36/FAT: fatty acid translocase; ER: endoplasmic reticulum; iNOS: inducible nitric oxide synthase; UCP: uncoupling protein; NPC1L1: Niemann-Pick C1-Like 1; VAT: visceral AT; FA: fatty acid; AMPK: adenosine monophosphate-activated protein kinase; AOX1: aldehyde oxidase 1; CD40: cluster of differentiation 40; sICAM-1: soluble intracellular adhesion molecule-1; HDLs: high-density lipoproteins; PUFAs: n-3 polyunsaturated fatty acids.