Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. They play critical roles in various biological processes, including metabolism, cellular differentiation, inflammation, and energy homeostasis.
There are three main types of PPARs:
- PPAR-alpha (PPARα)
- PPAR-beta/delta (PPARβ/δ)
- PPAR-gamma (PPARγ)
Each type has distinct tissue distribution and functions:
- PPAR-alpha is primarily involved in lipid metabolism, particularly fatty acid oxidation, and is abundantly expressed in the liver, heart, and skeletal muscle.
- PPAR-beta/delta is broadly expressed and plays roles in lipid metabolism, glucose homeostasis, and cell proliferation.
- PPAR-gamma is mainly known for its involvement in adipocyte differentiation and lipid storage, but it also regulates glucose metabolism and inflammation. It is predominantly expressed in adipose tissue, where it regulates adipogenesis and insulin sensitivity.
PPARs are activated by ligands, which include fatty acids and their derivatives, as well as synthetic agonists such as thiazolidinediones (TZDs) used in the treatment of type 2 diabetes. Upon activation, PPARs heterodimerize with retinoid X receptors (RXRs) and bind to specific DNA sequences called PPAR response elements (PPREs) in the promoter regions of target genes, leading to changes in gene expression.
Because of their roles in metabolism and inflammation, PPARs are therapeutic targets for various diseases, including metabolic disorders (e.g., dyslipidemia, insulin resistance, and type 2 diabetes), cardiovascular diseases, and inflammatory conditions.
