The PPARα and PPARγ Epigenetic Landscape in Cancer and Immune and Metabolic Disorders

Int J Mol Sci. 2021 Sep 30;22(19):10573. doi: 10.3390/ijms221910573.

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-modulated nuclear receptors that play pivotal roles in nutrient sensing, metabolism, and lipid-related processes. Correct control of their target genes requires tight regulation of the expression of different PPAR isoforms in each tissue, and the dysregulation of PPAR-dependent transcriptional programs is linked to disorders, such as metabolic and immune diseases or cancer. Several PPAR regulators and PPAR-regulated factors are epigenetic effectors, including non-coding RNAs, epigenetic enzymes, histone modifiers, and DNA methyltransferases. In this review, we examine advances in PPARα and PPARγ-related epigenetic regulation in metabolic disorders, including obesity and diabetes, immune disorders, such as sclerosis and lupus, and a variety of cancers, providing new insights into the possible therapeutic exploitation of PPAR epigenetic modulation.

Keywords: DNA methylation; PPARs; cancer; diabetes; histone modification; immunity; miRNA; obesity.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA Methylation
  • Epigenesis, Genetic*
  • Gene Expression Regulation
  • Humans
  • Immune System Diseases / genetics*
  • Immune System Diseases / metabolism
  • Immune System Diseases / therapy
  • Metabolic Diseases / genetics*
  • Metabolic Diseases / metabolism
  • Metabolic Diseases / therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / therapy
  • PPAR alpha / genetics*
  • PPAR alpha / metabolism
  • PPAR gamma / genetics*
  • PPAR gamma / metabolism

Substances

  • PPAR alpha
  • PPAR gamma