Drugs Involved in Dyslipidemia and Obesity Treatment: Focus on Adipose Tissue
Schematic illustration of the main intracellular pathways and the effects of drugs used in dyslipidemia and obesity in (A) differentiation of preadipocytes into mature adipocytes. This process is on dependence of the PKA pathway, which activates transcriptional factors such as C/EBPB, C/EBPd, C/EBPa, and PPARG that ultimately lead to increase of adipogenesis gene expression. Statins and liraglutide inhibit adipogenesis while niacin and fibrates stimulate, by inducing upregulation of adipogenesis genes (leptin; adiponectin, FABP4, perilipin, and GLUT4, SCD1) expression and (B) immune and endocrine functions of WAT. Adipocyte exerts autocrine and paracrine actions, through secreting adipokines and also endocrine actions in distant organs. Most of the drugs exhibit an anti-inflammatory role through modulation of adipokine expression. Through modulation of leucocyte chemotaxis, they also affect NK cell activity and macrophage phagocytosis. See text for more details. →: stimulates; ⊣: inhibits; AC: adenylyl cyclase; cAMP: cyclic adenosine monophosphate; PKA: cAMP-dependent protein kinase A; C/EBP: CCATT enhancer-binding proteins; PPARs: peroxisome proliferator-activated receptors; SREBP1: sterol regulatory element-binding protein-1; RXTα: retinoid X receptor-α; SRE: sterol response elements; SRB1: scavenger receptor 1; NK cells: natural killer cells; CD40: cluster of differentiation 40; CD40L: CD40 ligand; 11B-HSD1: 11B-Hydroxysteroid dehydrogenase type 1; TNFα: tumour necrosis factor α; IL: interleukin; CCL2 or MCP1: CC-chemokine ligand 2; PAI-1: plasminogen activator inhibitor type 1; AdipoR: adiponectin receptor; IL1RA: IL1 receptor antagonist; IFN-γ: interferon-γ; TLR: Toll-like receptors; NFκB: nuclear factor kappa B; SRB1: scavenger receptor 1; VCAM1: vascular cell adhesion molecule-1; E-selectin: endothelial-leukocyte adhesion molecule-1; ICAM1: intracellular adhesion molecule-1; OBRb: leptin receptor; ERK: extracellular signal-regulated kinase; MAPK: p38 mitogen-activated protein kinases; iNOS: inducible nitric oxide synthase; ROS: reactive oxygen species; TNFR: TNF receptor; IKKB: NFκB kinase-B; JNK: Jun N-terminal kinase; ER: endoplasmic reticulum; IR: insulin receptor (IR); IRS: insulin receptor substrate; UCP: uncoupling protein; CAP1: adenylyl cyclase-associated protein 1; ET1: endothelin-1.