World Library  
Flag as Inappropriate
Email this Article

PPAR agonist

Article Id: WHEBN0018775143
Reproduction Date:

Title: PPAR agonist  
Author: World Heritage Encyclopedia
Language: English
Subject: Linagliptin, Colestilan, Insulin (medication), Pharmacology, Transcription factors
Publisher: World Heritage Encyclopedia

PPAR agonist

PPAR-alpha and-gamma pathways

PPAR agonists are drugs which act upon the peroxisome proliferator-activated receptor. They are used for the treatment of symptoms of the metabolic syndrome, mainly for lowering triglycerides and blood sugar.


PPAR-alpha and PPAR-gamma are the molecular targets of a number of marketed drugs. The main classes of PPAR agonists are:

PPAR-alpha agonists

PPARα (alpha) is the main target of fibrate drugs, a class of amphipathic carboxylic acids (clofibrate, gemfibrozil, ciprofibrate, bezafibrate, and fenofibrate). They were originally indicated for cholesterol disorders and more recently for disorders that feature high triglycerides. Many of them increase the risk of cancer to the point where they eliminate the survival benefit of reduced heart disease.

PPAR-gamma agonists

PPARγ (gamma) is the main target of the drug class of thiazolidinediones (TZDs), used in diabetes mellitus and other diseases that feature insulin resistance. It is also mildly activated by certain NSAIDs (such as ibuprofen) and indoles, as well as from a number of natural compounds.[1][2] Known inhibitors include the experimental agent GW-9662.

They are also used in treating hyperlipidaemia in atherosclerosis. Here they act by increasing the expression of ABCA1, which transports extra-hepatic cholesterol into HDL. Increased uptake and excretion from the liver therefore follows.

Animal studies have shown their possible role in amelioration of pulmonary inflammation, especially in asthma.[3]

They may cause fluid retention and heart failure in those with weak hearts.

PPAR-delta agonists

PPARδ (delta) is the main target of a research chemical named GW501516. It has been shown that agonism of PPARδ changes the body's fuel preference from glucose to lipids,[4] but ironically improves metabolic syndrome (which is characterized by the body being unable to efficiently deal with glucose resulting in insulin resistance and sometimes diabetes).

Dual and pan PPAR agonists

A fourth class of dual PPAR agonists, so-called glitazars, which bind to both the α and γ PPAR isoforms, are currently under active investigation for treatment of a larger subset of the symptoms of the metabolic syndrome.[5][6] These include the experimental compounds aleglitazar, muraglitazar and tesaglitazar. In June 2013, saroglitazar was the first glitazar to be approved for clinical use.[7]

In addition, there is continuing research and development of new dual α/δ and γ/δ PPAR agonists for additional therapeutic indications, as well as "pan" agonists acting on all three isoforms.[8][9]


  1. ^ Atanasov AG, Wang JN, Gu SP, Bu J, Kramer MP, Baumgartner L, Fakhrudin N, Ladurner A, Malainer C, Vuorinen A, Noha SM, Schwaiger S, Rollinger JM, Schuster D, Stuppner H, Dirsch VM, Heiss EH. Honokiol: a non-adipogenic PPARγ agonist from nature. Biochim Biophys Acta. 2013 Oct;1830(10):4813-9. doi: 10.1016/j.bbagen.2013.06.021. PubMed PMID: 23811337; PubMed Central PMCID: PMC3790966.
  2. ^ Atanasov AG, Blunder M, Fakhrudin N, Liu X, Noha SM, Malainer C, Kramer MP, Cocic A, Kunert O, Schinkovitz A, Heiss EH, Schuster D, Dirsch VM, Bauer R. Polyacetylenes from Notopterygium incisum--new selective partial agonists of peroxisome proliferator-activated receptor-gamma. PLoS One. 2013 Apr 22;8(4):e61755. doi: 10.1371/journal.pone.0061755. Print 2013. PubMed PMID: 23630612; PubMed Central PMCID: PMC3632601.
  3. ^ Gu, M. X.; Liu, X. C.; Jiang, L (2013). "Effect of peroxisome proliferator-activated receptor-gamma on proliferation of airway smooth muscle cells in mice with asthma". Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 15 (7): 583–7.  
  4. ^ B. Brunmair et al. (2006). "Activation of PPAR-δ in isolated rat skeletal muscle switches fuel preference from glucose to fatty acids". Diabetologia 49 (11): 2713–22.  
  5. ^ Fiévet C, Fruchart JC, Staels B (2006). "PPARalpha and PPARgamma dual agonists for the treatment of type 2 diabetes and the metabolic syndrome". Current Opinion in Pharmacology 6 (6): 606–14.  
  6. ^ Balakumar P, Rose M, Ganti SS, Krishan P, Singh M (2007). "PPAR dual agonists: are they opening Pandora's Box?". Pharmacol. Res. 56 (2): 91–8.  
  7. ^ (German)
  8. ^ Staels B, Fruchart JC (2005). "Therapeutic roles of peroxisome proliferator-activated receptor agonists". Diabetes 54 (8): 2460–70.  
  9. ^ Nevin DK, Fayne D, Lloyd DG (2011). "Rational targeting of peroxisome proliferating activated receptor subtypes". Current Medicinal Chemistry 11 (36): 5598–623.  
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.

Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.