The context-dependent roles of PPAR-γ in adipocyte differentiation and obesity: a master regulator with dual functions

Obesity has become a global public health crisis. It is characterized by pathological proliferation of adipose tissue resulting from an energy metabolism imbalance. Adipocyte differentiation is the core process driving this proliferation and is tightly regulated by a complex molecular network. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is the primary regulator of adipocyte differentiation. It also plays a key regulatory role in lipid and glucose metabolism as well as inflammatory responses. Its dysregulation is closely associated with the onset and progression of obesity. This review goes beyond a descriptive summary of PPAR-γ's role in adipogenesis and instead focuses on the context-dependent roles of this factor in the pathophysiology of obesity. This article maps the upstream and downstream molecular networks regulating PPAR-γ activity. It also analyzes the dual and even opposing functions that PPAR-γ exhibits under different physiological and pathological conditions. By integrating cutting-edge research advances, this review further elucidates the tissue-specific mechanisms of PPAR-γ and evaluates the therapeutic potential of targeting this pathway in obesity interventions. This review aims to provide a theoretical framework for understanding the mechanisms by which PPAR-γ dysfunction contributes to the development of obesity. It offers a reference for the development of precision treatment strategies for obesity and related metabolic diseases.