Pathological remodeling of adipose tissue in polycystic ovary syndrome (PCOS): Adipokine-Cytokine crosstalk at the interface of metabolism and reproduction

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine-metabolic and reproductive disorder affecting approximately 10-13% of women globally, although prevalence varies according to the diagnostic criteria and population studied. Emerging evidence identifies adipose tissue as an important endocrine and immune mediator of PCOS pathophysiology. In women with PCOS, adipose depots undergo maladaptive remodeling characterized by adipocyte hypertrophy, extracellular matrix (ECM) fibrosis, impaired angiogenesis, and immune cell infiltration. These changes disrupt metabolic flexibility, promote chronic low-grade inflammation, and alter systemic energy regulation. A critical component of this pathology is the crosstalk between adipokines and cytokines, which serves as a mechanistic bridge between metabolic disturbances and reproductive impairment. Dysregulation of leptin, adiponectin, chemerin, visfatin, and resistin, coupled with overexpression of pro-inflammatory cytokines such as tumour necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, perpetuates insulin resistance (IR), hyperinsulinemia, and oxidative stress (OS). These interactions directly impair ovarian folliculogenesis, granulosa-theca cell function, and hypothalamic-pituitary-gonadal (HPG) signaling, thereby contributing to anovulation, hyperandrogenism, and subfertility. This narrative review critically synthesizes histopathological, molecular, and translational evidence linking pathological adipose remodeling to PCOS. It further explores the potential of adipokines and cytokines as biomarkers and discusses emerging therapeutic strategies to restore adipose homeostasis. Understanding adipose-immune-reproductive interactions offers new opportunities for precision medicine approaches, with the potential to transform PCOS management from symptomatic control to long-term disease modification.