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The role of peroxisome proliferator-activated receptors (PPARs)
What are PPARs?
- PPARs are nuclear receptor transcription factors that regulate lipid and glucose metabolism in the body.[1]
- There are three types of PPARs[1]
- Each PPAR is expressed differently in various tissues and plays different metabolic roles in the body.[1]
- Despite their functional and locational differences, PPARs share the same general structure and molecular mechanism of action.[1]
General PPAR structure
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PPAR mechanism of action
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Each PPAR is unique[1,2]
PPAR
- Expressed in:
- Liver
- Heart
- Skeletal muscle
- Activates gene expression that results in:
- Fatty acid oxidation
- Ketone body synthesis
- Glucose sparing
PPAR
- Expressed in:
- Adipose tissue
- Lower intestine
- Immune cells
- Activates gene expression that results in:
- Adipocyte differentiation
- Lipid metabolism
- Glucose utilization
PPAR
- Expressed:
- Ubiquitously throughout the body
- Activates gene expression that results in:
- Fatty acid oxidation where PPARα is absent
To view a video on the similarities and differences between PPAR ligands, click here.
PPAR ligands can demonstrate antiatherogenic effects
- PPAR ligands are small molecules that bind with PPARs, resulting in PPAR activity regulation.[1]
- PPAR ligands have been shown to prevent:
- Endothelial cell inflammation[3]
- Leukocyte-endothelial cell interactions[4]
- Macrophage foam cell formation[5]
- Mitogen-induced smooth muscle proliferation and migration[6]
- Cholesterol from staying in the cell[5]
- All of these have been shown to be contributing factors to atherosclerosis.[7]
Modulation of atherosclerosis by the effects of PPARs on target genes[8,9]
- Through regulation of the genes listed above, PPARs may have an impact on several portions of atherogenesis development.
Read more.
References: 1. Ferré P. The biology of peroxisome proliferator–activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes. 2004;53(suppl 1):S43-S50. 2. Sharma AM, Staels B. Peroxisome proliferator-activated receptor gamma and adipose tissue—understanding obesity-related changes in regulation of lipid and glucose metabolism. J Clin Endocrinol Metab. 2007;92:386-395. 3. Marx N, Mach F, Sauty A, et al. Peroxisome proliferator-activated receptor-gamma activators inhibit IFN-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells. J Immunol. 2000;164:6503-6508. 4. Jackson SM, Parhami F, Xi XP, et al. Peroxisome proliferator–activated receptor activators target human endothelial cells to inhibit leukocyte–endothelial cell interaction. Arterioscler Thromb Vasc Biol. 1999;19:2094-2104. 5. Li AC, Binder CJ, Gutierrez A, et al. Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARα, β/gamma, and delta. J Clin Invest. 2004;114:1564-1576. 6. Law RE, Goetze S, Xi XP, et al. Expression and function of PPARgamma in rat and human vascular smooth muscle cells. Circulation. 2000;101:1311-1318. 7. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115-126. 8. Barbier O, Torra IP, Duguay Y, et al. Pleiotropic actions of peroxisome proliferator–activated receptors in lipid metabolism and atherosclerosis. Arterioscler Thromb Vasc Biol. 2002;22:717-726. 9. Marx N, Duez H, Fruchart JC, Staels B. Peroxisome proliferator-activated receptors and atherogenesis: regulators of gene expression in vascular cells. Circ Res. 2004;94:1168-1178.
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