PPAR Agonists and Metabolic Syndrome: An Established Role?

Int J Mol Sci. 2018 Apr 14;19(4):1197. doi: 10.3390/ijms19041197.


Therapeutic approaches to metabolic syndrome (MetS) are numerous and may target lipoproteins, blood pressure or anthropometric indices. Peroxisome proliferator-activated receptors (PPARs) are involved in the metabolic regulation of lipid and lipoprotein levels, i.e., triglycerides (TGs), blood glucose, and abdominal adiposity. PPARs may be classified into the α, β/δ and γ subtypes. The PPAR-α agonists, mainly fibrates (including newer molecules such as pemafibrate) and omega-3 fatty acids, are powerful TG-lowering agents. They mainly affect TG catabolism and, particularly with fibrates, raise the levels of high-density lipoprotein cholesterol (HDL-C). PPAR-γ agonists, mainly glitazones, show a smaller activity on TGs but are powerful glucose-lowering agents. Newer PPAR-α/δ agonists, e.g., elafibranor, have been designed to achieve single drugs with TG-lowering and HDL-C-raising effects, in addition to the insulin-sensitizing and antihyperglycemic effects of glitazones. They also hold promise for the treatment of non-alcoholic fatty liver disease (NAFLD) which is closely associated with the MetS. The PPAR system thus offers an important hope in the management of atherogenic dyslipidemias, although concerns regarding potential adverse events such as the rise of plasma creatinine, gallstone formation, drug-drug interactions (i.e., gemfibrozil) and myopathy should also be acknowledged.

Keywords: PPARs; elafibrinor; metabolic syndrome; pemafibrate.

Publication types

  • Review

MeSH terms

  • Animals
  • Benzoxazoles / chemistry
  • Benzoxazoles / pharmacology
  • Benzoxazoles / therapeutic use
  • Butyrates / chemistry
  • Butyrates / pharmacology
  • Butyrates / therapeutic use
  • Chalcones / chemistry
  • Chalcones / pharmacology
  • Chalcones / therapeutic use
  • Drug Discovery*
  • Humans
  • Hypoglycemic Agents / chemistry
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Hypolipidemic Agents / chemistry
  • Hypolipidemic Agents / pharmacology*
  • Hypolipidemic Agents / therapeutic use
  • Insulin Resistance
  • Lipid Metabolism / drug effects
  • Lipids / blood*
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / metabolism
  • Peroxisome Proliferator-Activated Receptors / agonists*
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Propionates / chemistry
  • Propionates / pharmacology
  • Propionates / therapeutic use
  • Thiazolidinediones / chemistry
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use
  • Triglycerides / blood
  • Triglycerides / metabolism


  • (R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid
  • 2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid
  • Benzoxazoles
  • Butyrates
  • Chalcones
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Lipids
  • Peroxisome Proliferator-Activated Receptors
  • Propionates
  • Thiazolidinediones
  • Triglycerides