PPAR: Mechanisms of Action and Regulation

What happens to the positioning of H12 when a ligand binds to PPARγ?

PPARγ ubiquitination leads to an increase in transcriptional activity.

What is the role of SIRT1 in PPARγ-mediated browning of white adipose tissue?

PPARγ regulates lipid metabolism and glucose homeostasis by increasing the expression of genes such as _______________________.

Match the following post-translational modifications of PPARγ with their effects on its activity:

Ligand Binding and Co-regulator Switching

Ligand binding induces a change in the positioning of H12, favoring co-activator binding and leading to co-repressor/co-activator switching.

Post-translational Modification of PPAR

Phosphorylation of PPAR: • Can be kinase-dependent (e.g., Ser112) • Alters transcriptional activity
SUMOylation of PPAR: • Blocks transcriptional activity (e.g., Lys107)
Ubiquitination of PPAR: • Leads to degradation of PPAR
Acetylation of PPAR: • Deacetylation by SIRT1 is necessary for PPAR-mediated browning of white adipose tissue

PPARγ and Insulin Sensitivity

PPARγ plays a role in: • Adipocyte differentiation and mature adipocyte function • Lipid metabolism • Glucose homeostasis
PPARγ increases expression of genes involved in: • Glucose uptake: Glut4 • Insulin signaling: PI3K, CAP, IRS-1/IRS2 • All these genes are important participants in the activation of insulin receptor
Induced transducers for PPARγ: • FGF1 and FGF21 act locally to increase PPARγ

This quiz covers the mechanisms of action and regulation of PPAR, including ligand binding, post-translational modifications, and their effects on transcriptional activity and insulin sensitivity.