Epigenetic codes of PPARγ in metabolic disease

Peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-regulated nuclear hormone receptor, plays critical roles in metabolism and adipogenesis. PPARγ ligands such as thiazolidinediones (TZDs) exert insulin sensitizing and anti-inflammatory effects primarily through action on adipocytes, and are thus widely used to treat metabolic syndrome, especially type II diabetes. A number of PPARγ interacting partners have been identified, many of which are known epigenetic regulators, including enzymes for histone acetylation/deacetylation and histone methylation/demethylation. However, their functional roles in the PPARγ transcriptional pathway are not well defined. Recent advances in ChIP-based and deep sequencing technology are revealing previously underappreciated epigenomic mechanisms and therapeutic potentials of this nuclear receptor pathway.

► Anti-diabetic TZD class of drugs targets PPARγ primarily through effects in adipocytes.
► Many PPARγ interacting proteins possess epigenetic activities.
► Recent technical advance in ChIP-based whole genome analysis uncovers novel epigenomic mechanisms.
► Understanding precise epigenetic regulation of PPARγ should facilitate potential therapeutic approaches.