Drugs Involved in Dyslipidemia and Obesity Treatment: Focus on Adipose Tissue

Table 1

Drugs used in dyslipidemia: classical effects, effects on adipose tissue, and weight.

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.