Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) is a ligand-activated nuclear receptor that plays a crucial role in the regulation of lipid and glucose homeostasis, inflammation, and cellular differentiation . It is a member of the nuclear receptor family and is involved in various physiological processes, including adipogenesis, insulin sensitivity, and vascular homeostasis .
PPAR-γ was first identified in the early 1990s and has since been extensively studied for its role in adipocyte differentiation, maintenance, and function . The receptor has four functional domains: the N-terminal A/B domain, the DNA binding domain (DBD), the hinge domain, and the C-terminal ligand binding domain (LBD) . The LBD is responsible for ligand specificity and is crucial for homo- or hetero-dimerization, allowing interaction with co-repressors, coactivators, and other cofactors .
PPAR-γ acts through the formation of heterodimers with retinoid X receptors (RXRs) to modify target gene expression at the transcriptional level in response to endogenous or synthetic ligands . When activated by its ligand, PPAR-γ can interact with specific DNA response elements to control gene transcription and expression . This regulation is essential for lipid metabolism, improving insulin sensitivity, modulating antitumor mechanisms, reducing oxidative stress, and inhibiting inflammation .
PPAR-γ has been shown to have significant therapeutic potential in various medical conditions. It has been studied for its neuroprotective effects in cerebral ischemic injury, where it helps prevent post-ischemic inflammation and neuronal damage . Additionally, PPAR-γ agonists have shown therapeutic effects in kidney conditions and various cancers . However, the associated side effects of synthetic agonists restrict their widespread use .
Recombinant human PPAR-γ is produced using molecular cloning and transient expression techniques. One such method involves the use of an inducible Tet-On 3G system in human embryonic kidney 293T (HEK293T) cells . This system allows for high expression levels of PPAR-γ, making it a valuable model for studying the receptor’s function and potential therapeutic applications .