Schematic illustration of the main intracellular pathways underlying WAT metabolic functions and the effects of drugs used in dyslipidemia and obesity on these pathways: B-oxidation
through upregulation of ACS, CD36, MCD, and CPT1 genes and after stimulus as PPARα
agonist or adrenergic agonists, through upregulation of the AMPK pathway); lipolysis
(sequentially by ATGL, HSL, and MGL actions); lipogenesis
through upregulation of GLUT4; ACC genes). Statins induce adipocyte FA uptake, increasing LPL expression, while decreasing cholesterol release.
Only in obese models, statins stimulate lipogenesis de novo; globally, fibrates inhibit lipogenesis and stimulate FA oxidation and thermogenesis (
through upregulation of PRDM16, PPAR-γ
, and UCP-1 gene expression); niacin inhibits lipolysis and increases lipogenesis gene expression; orlistat enhances TG degradation. See text for more details. →: stimulates; ⊣: inhibits; TG: triglycerides; FA: fatty acid; Ch: cholesterol; LPL: lipoprotein lipase; VLDL: very low-density lipoproteins; DGAT: diacylglycerol acyltransferase; ACC: enzyme acetyl-coenzyme A carboxylase; SREBP1: sterol regulatory element-binding protein 1; ChREBP: carbohydrate response element-binding protein; GLUT4: glucose transporter type 4; PI3-K: phosphoinositide 3-kinase dependent; PDE3B: phosphodiesterase 3B; AC: adenylyl cyclase; cAMP: cyclic adenosine monophosphate; PKA: cAMP-dependent protein kinase A; PKB/Akt: protein kinase B; GC activity: guanylyl cyclase activity; cGMP: cyclic guanosine monophosphate; PKG: cGMP-dependent protein kinase; ATGL: adipocyte triglyceride lipase; HSL: hormone-sensitive lipase; MGL: monoacylglycerol lipase; PPARs: peroxisome proliferator-activated receptors; PGC-1a: peroxisome proliferator-activated receptor G coactivator 1; ACS: acyl-CoA synthetase; CD36/FAT: fatty acid translocase; CPT1: carnitine palmitoyl transferase 1; AR: adrenoceptors; ANP/BNP: atrial or brain natriuretic peptide; NPR-A: natriuretic receptor A; IR: insulin receptor; IRS: insulin receptor substrate; AMPK: adenosine monophosphate-activated protein kinase; SIRT1: sirtuin 1; BAT: brown adipose tissue; HDLs: high-density lipoproteins; LXRα
: liver X receptor alpha; ABCA1 transporter: ATP-binding cassette A1 transporter; SRB1: scavenger-receptor 1.