title: New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Novel peroxisome proliferator-activated receptor (PPAR) modulators (selective PPAR modulators [SPPARMs]) and dual PPAR agonists may have an important role in the treatment of cardiometabolic disorders owing to lipid-modifying, insulin-sensitizing and anti-inflammatory effects.
  
  
  METHODS
  This review summarizes the efficacy of new PPAR agonists and SPPARMs that are under development for the treatment of atherogenic dyslipidemia and non-alcoholic fatty liver disease (NAFLD).
  
  
  CONCLUSIONS
  ABT-335 is a new formulation of fenofibrate that has been approved for concomitant use with statins. K-877, a SPPARM-α with encouraging preliminary results in modulating atherogenic dyslipidemia, and INT131, a SPPARM-γ with predominantly insulin-sensitizing actions, may also have favorable lipid-modifying effects. Although the development of dual PPAR-α/γ agonists (glitazars) and the SPPARM-δ GW501516 has been abandoned because of safety issues, another SPPARM-δ (MBX-8025) and a dual PPAR-α/δ agonist (GFT-505) have shown promising efficacy in decreasing plasma triglyceride and increasing high-density lipoprotein cholesterol concentrations, as well as improving insulin sensitivity and liver function. The beneficial effects of GFT-505 are complemented by preclinical findings that indicate reduction of hepatic fat accumulation, inflammation and fibrosis, making it a promising candidate for the treatment of NAFLD/nonalcoholic steatohepatitis (NASH). Long-term trials are required to test the efficacy and safety of these new PPAR agonists in reducing cardiovascular outcomes and treating NAFLD/NASH.
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences , Mashhad , Iran.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.forename: Gerard T
authors.initials: GT
authors.lastname: Chew
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D000085:Acetates / Q000627:therapeutic use; D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control*; D047188:Chalcones / Q000627:therapeutic use; D008076:Cholesterol, HDL / Q000097:blood; D050171:Dyslipidemias / Q000188:drug therapy* / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism; D011345:Fenofibrate / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007333:Insulin Resistance; D008075:Lipoproteins, HDL / Q000097:blood; D065626:Non-alcoholic Fatty Liver Disease; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000378:metabolism; D011422:Propionates / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D014230:Triazoles / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
chemical_list: C572244:(2-methyl-4-(5-methyl-2-(4-trifluoromethyl-phenyl)-2H-(1,2,3)triazol-4-ylmethylsulfanyl)phenoxy)acetic acid; C585906:2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid; C533234:2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoic acid; D000085:Acetates; D047188:Chalcones; D008076:Cholesterol, HDL; C425931:GW 501516; C541917:INT 131; D008075:Lipoproteins, HDL; D047492:Peroxisome Proliferator-Activated Receptors; D011422:Propionates; D011804:Quinolines; D013449:Sulfonamides; D013844:Thiazoles; D014230:Triazoles; D014280:Triglycerides; D011345:Fenofibrate