PPAR Signaling Pathway

About PPAR Pathway

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors, which are responsible for regulating gene expression. PPARs are firstly found in the Xenopus frog as nuclear receptors, which induce the proliferation of peroxisomes in the cells. They perform multiple functions like cellular respiration, metabolism, differentiation and development. In addition, because they play an important role in lipid and glucose homeostasis, they are called lipid and insulin sensors. The PPAR family genes comprised of three isoforms PPAR-α, PPAR-β/δ and PPAR-γ, which are expressed in the different tissues in various species including the human. PPAR-α mainly influences fatty acid metabolism and its activation lowers lipid levels, while PPAR-γ is mostly involved in the regulation of the adipogenesis, energy balance, and lipid biosynthesis. PPAR-β/δ participates in fatty acid oxidation, mostly in skeletal and cardiac muscles, but it also regulates blood glucose and cholesterol levels. Like other nuclear receptors, PPARs are modular in structure and contain the following functional domains: (A/B) N-terminal region, (C) DBD (DNA-binding domain), (D) flexible hinge region, (E) LBD (ligand binding domain), (F) C-terminal region. PPARα and PPAR-γ are the molecular targets of several marketed drugs. For instance, the hypolipidemic fibrates activate PPARα, and the anti-diabetic thiazolidinediones activate PPAR-γ. The synthetic chemical perfluorooctanoic acid activates PPARα while the synthetic perfluorononanoic acid activates both PPAR-α and PPAR-γ. Berberine activates PPAR-γ, as well as other natural compounds from different chemical classes.

Overview of PPAR signaling pathway

Associated Diseases

Related Pathways

1. Agarwal, Swati, Anuradha Yadav, and Rajnish Kumar Chaturvedi. "Peroxisome proliferator-activated receptors (PPARs) as therapeutic target in neurodegenerative disorders." Biochemical and biophysical research communications 483.4 (2017): 1166-1177.
2. Grygiel-Górniak, Bogna. "Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications-a review." Nutrition journal 13.1 (2014): 17.
3. Derosa, Giuseppe, Amirhossein Sahebkar, and Pamela Maffioli. "The role of various peroxisome proliferator‐activated receptors and their ligands in clinical practice." Journal of cellular physiology 233.1 (2018): 153-161.
4. Atanasov, Atanas G., et al. "Honokiol: a non-adipogenic PPARγ agonist from nature." Biochimica et Biophysica Acta (BBA)-General Subjects 1830.10 (2013): 4813-4819.
5. Atanasov, Atanas G., et al. "Polyacetylenes from Notopterygium incisum–new selective partial agonists of peroxisome proliferator-activated receptor-gamma." PLoS One 8.4 (2013): e61755.

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