The Role of PPAR-δ in Metabolism, Inflammation, and Cancer: Many Characters of a Critical Transcription Factor

Int J Mol Sci. 2018 Oct 26;19(11):3339. doi: 10.3390/ijms19113339.


Peroxisome proliferator-activated receptor-delta (PPAR-δ), one of three members of the PPAR group in the nuclear receptor superfamily, is a ligand-activated transcription factor. PPAR-δ regulates important cellular metabolic functions that contribute to maintaining energy balance. PPAR-δ is especially important in regulating fatty acid uptake, transport, and β-oxidation as well as insulin secretion and sensitivity. These salutary PPAR-δ functions in normal cells are thought to protect against metabolic-syndrome-related diseases, such as obesity, dyslipidemia, insulin resistance/type 2 diabetes, hepatosteatosis, and atherosclerosis. Given the high clinical burden these diseases pose, highly selective synthetic activating ligands of PPAR-δ were developed as potential preventive/therapeutic agents. Some of these compounds showed some efficacy in clinical trials focused on metabolic-syndrome-related conditions. However, the clinical development of PPAR-δ agonists was halted because various lines of evidence demonstrated that cancer cells upregulated PPAR-δ expression/activity as a defense mechanism against nutritional deprivation and energy stresses, improving their survival and promoting cancer progression. This review discusses the complex relationship between PPAR-δ in health and disease and highlights our current knowledge regarding the different roles that PPAR-δ plays in metabolism, inflammation, and cancer.

Keywords: PPAR-δ; cancer; inflammation; β-oxidation metabolism.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / metabolism
  • Dyslipidemias / immunology
  • Dyslipidemias / metabolism
  • Fatty Liver / immunology
  • Fatty Liver / metabolism
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Insulin Resistance
  • Metabolic Syndrome / immunology
  • Metabolic Syndrome / metabolism
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • PPAR delta / immunology
  • PPAR delta / metabolism*


  • PPAR delta