Table 1.
Main characteristics of PPAR subtypes.
| PPAR Subtype | PPARα | PPAR β/δ | PPARγ |
|---|---|---|---|
| Gene location | Human chromosome 22q12.2–13.1 | Human chromosome 6p21.1–21.2 | Human chromosome 3p25 |
| Isoforms | None | None | PPARγ1, PPARγ2, PPARγ3 |
| Tissue distribution | Liver, heart, skeletal muscle (tissues with high fatty acid oxidation rates); brown adipose tissue, kidney, adrenal gland. | Liver, kidney, skeletal and cardiac muscle, adipose tissue, brain, colon, vasculature, esophagus, gut. Ubiquitous. | Mainly in adipose tissue (white and brown). Other tissues such as liver, gut, kidney, retina, immunologic system, muscles, spleen, urinary bladder, heart, lung, brain, vasculature. |
| Endogenous Ligands | Unsaturated and saturated fatty acids and their derivatives (8-S-hydroxyeicosatetraenoic acid, arachidonic acid lipoxygenase metabolite LTB4, arachidonate monooxygenase metabolite epoxyeicosatrienoic acids), leukotriene derivatives, VLDL hydrolysis products. | Unsaturated fatty acids, arachidonic acid cyclooxygenase metabolite prostacyclin, the linoleic acid 15-lipoxygenase-1 product 13-S-hydroxyoctadecadienoic acid, carbaprostacyclin, components of VLDL. | Polyunsaturated fatty acids, prostanoids (15-deoxy-Δ12, 14-prostaglandin J2 (15-dPGJ2)), 13-hydroxyeicosatetraenoic acid, components of oxidized LDL, eicosanoids, oxidized alkyl phospholipids. |
| Functions | Major regulator of the mitochondrial and peroxisomal β-oxidation (fatty acid metabolism), lowers lipid levels, anti-inflammatory activities. |
Increase lipid catabolism, improves the plasma HDL-cholesterol levels and insulin resistance, induce cell proliferation and differentiation, anti-inflammatory activities. |
Regulate adipocyte differentiation, lipid storage, and glucose metabolism (improves insulin sensitivity), main regulator of metabolic genes, increase fatty acid oxidation, HDL and uncoupling protein, decrease triglycerides, improves vascular integrity, energy balance, anti-inflammatory activities. |
| Target genes | CYP8B1, FATP, FAT/CD36, liver cytosolic FABP, LPL. Lipid/hormone transport genes. (LEPR, SLC27A2, SLC27A4). Acyl-CoA metabolism. (ACOT12, ACSL3, ACSL3, ACSL5, ACSL1, ACSM3, FABP1, FABP3). β-oxidation. (ACAA2, ACADM, ACADS, ACADVL, CPT1A, CPT2, ETFDH, HADHA, HADHB, SLC25A20, SLC22A5, TXNIP). Ketogenesis/ketolysis genes. (FGF21, HMGCS2), Peroxisomal β-oxidation (ABCD2, ABCD3, ACAA1A, ACOX1, ECH1, HSD17B4). Lipogenesis. (ACACB, AGPAT2, ELOVL5, ELOVL6 FADS1, GPAM, MLYCD, MOD1). Lipases and lipid droplet proteins. (ADFP, CIDEC, PNPLA2, S3-12). Lipoprotein metabolism. (ANGPTL4, APOA1, APOA2, APOA5, APOCIII, LIPC, PCTP, VLDLR). Cholesterol and bile metabolism. (ABCA1, ABCB4, CYP7A1, FXR, LXR) |
Genes related with lipid uptake, represses genes that participated in lipid metabolism and efflux. LPL, PGAR, IDK, PDK-1, Ubiquitin C, CPT1, AOX, LCAD, UCP1, UCP3, PGC1-alpha. Tumor angiogenesis (Pdgfrβ, Pdgfb, c-kit) |
AP2, CAP, IRS2, GLUT4, GLUT2, adiponectin, ACS, PCK2, LPL, FAT/CD36, FABP, GYK fatty acid transport, acyl-CoA synthetase, glucokinase, leptin, perilipin, GK PEPCK, UCP 1, UCP-2, UCP-3, LXR-alpha, TNF-alpha, IL-6. |
| References | [8,10,11,12,13,14,15] | [8,10,11,12,13,14,16,17] | [8,10,11,12,13,14,17,18,19,20] |
HDL, High density lipoprotein; LDL, low density lipoprotein; VLDL, Very low-density lipoprotein.