Minireview: PPARγ as the target of obesogens

Area of Science:

• Endocrinology
• Molecular Biology
• Toxicology

Background:

• Peroxisome proliferator-activated receptor gamma (PPARγ) is a crucial regulator of adipogenesis, impacting obesity and type II diabetes treatment.
• Obesogens are environmental chemicals linked to obesity, potentially acting through PPARγ activation.
• Tributyltin is a known PPARγ and RXR activator and the first identified obesogen with a clear mechanism.

Purpose of the Study:

• To explore the diverse mechanisms by which obesogens affect PPARγ and adipogenesis.
• To investigate both direct and indirect pathways, including ligand-independent actions, through which obesogens influence fat cell development.

Main Methods:

• Review of existing literature on PPARγ, adipogenesis, and obesogen mechanisms.
• Analysis of direct ligand-mediated activation of PPARγ.
• Examination of ligand-independent mechanisms, such as post-translational modifications and chromatin remodeling.

Main Results:

• Obesogens can activate PPARγ through direct ligand binding or indirectly via non-ligand mechanisms.
• Ligand-independent pathways include post-translational modifications and alterations in chromatin structure affecting PPARγ activity.
• PPARγ's role in multipotent stem cells highlights early developmental windows for obesogen influence on adipogenesis.

Conclusions:

• Obesogens can promote adipogenesis and obesity by targeting PPARγ through various direct and indirect mechanisms.
• Understanding these mechanisms, including ligand-independent actions, is vital for addressing obesity.
• Early developmental exposure to obesogens can permanently bias progenitor cells towards fat lineage via PPARγ modulation.