PPAR

In the field of molecular biology, the peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms.

FH535 sodium salt
1000998-59-3
BMS-687453
1000998-59-3
1014691-61-2
GSK0660
1014691-61-2
1048002-36-3
CS-7017 monohydrate
1048002-36-3
Parstatin (mouse)
1065756-01-5
1067214-81-6
GSK7227
1067214-81-6
108409-83-2
FH535
108409-83-2
111025-46-8
Pioglitazone
111025-46-8
B0084-081716
Oleylethanolamide
111-58-0
B0084-081792
Pioglitazone HCl
112529-15-4
B0084-284775
MSDC-0602
1133819-87-0
1168138-37-1
GSK1997132B
1168138-37-1
GW 1929 hydrochloride
1217466-21-1
122320-73-4
Rosiglitazone
122320-73-4
1338259-05-4
SR 1664
1338259-05-4

Background


An overview of PPAR

The peroxisome proliferator-activated receptors (PPARs) are a kind of ligand-activated receptors in the nuclear hormone receptor family that controls the metabolic processes in many cells and belong to ligand-inducible nuclear receptors. After PPARs combined with ligands are activated, they will form a heterodimer with retinoid x receptors (RXR). The resulting PPARγ/RXR heterodimer binds to the upstream PPAR reaction element (PPRE) of the target gene promoter and ultimately regulates the transcription of the target gene.

Major types of PPAR

PPARs consist of three subtypes: PPARα, PPARβ/δ, PPARγ. PPARα is highly expressed in the liver, skeletal muscle, kidney, heart and vascular wall, and is relatively low in fat and cartilage. PPARβ is widely expressed in vivo, and has a relatively high level of expression in the brain, stomach, and colon. PPARγ is an important cell differentiation transcription factor, which is expressed in mammalian adipose tissue, vascular smooth muscle tissue and myocardial tissue.

Activation of PPAR

There are two ligands for PPARs, including physiologic ligands and pharmacological ligands. Physiological ligands include 15-deoxidization prostaglandin J2 (15d-PGJ2), leukotriene (LTB4) and unsaturated fatty acid. Pharmacological ligands include Insulin sensitizing thiazolidinone compounds (TZDs), and fibrate having a value of treating cardiovascular diseases. Among them, the combination of 15d-PGJ2 and TZDS and PPARC has high affinity, and they are efficient ligands of PPARC. Fihmte and LTB4 are the efficient ligands of PPARA. When PPARs combines with Ligands, the PPARs can be activated to regulate the transcription activity of the target gene.

PPAR and diseases

PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms. And the PPAR family is mainly involved in fat metabolism and further participates in glucose metabolism. Studies have shown that PPARs can be used as a target for type II diabetes, regulating blood glucose and insulin sensitivity. For example, PPARC agonist can reduce blood sugar and glucose production in cells and increase insulin sensitivity of tolerant tissues without increasing intracellular glucose uptake and promoting insulin release. Other major related diseases include hyperlipidemia, inflammatory hernia (atherosclerosis), cancer (stomach and fat), and obesity.

References:

1. Liu ML, et al. (2001). A new progress in the study of peroxisome proliferation-activated receptor. Foreign Medical Sciences#Section of Pathophysiology and Clinical Medicine.