From the perspective of prolactin: a view on obesity

The physiological roles of prolactin extend beyond its classical functions in reproductive regulation. Emerging evidence indicates that prolactin is involved in energy homeostasis and may interact pathophysiologically with obesity; this has attracted increasing attention in endocrinology and metabolic research. Hyperprolactinemia (HPRL) is frequently observed in obese individuals. Observational studies have reported that weight-loss interventions are associated with reduced circulating prolactin levels, whereas dopamine agonists, which suppress prolactin secretion, improve metabolic and endocrine abnormalities in patients with established hyperprolactinemia. Accumulating evidence suggests an association between hyperprolactinemia and obesity. However, the directionality and causality of this relationship remain unclear. Experimental and translational studies suggest that elevated prolactin levels contribute to obesity-related phenotypes through multiple pathways, including altered central appetite regulation, modulation of adipocyte differentiation and lipid storage, impairment of insulin sensitivity, and disruption of the hypothalamic-pituitary-gonadal (HPG) axis. In contrast, obesity may be associated with increased circulating prolactin levels, which are potentially mediated by adipose tissue expansion, enhanced aromatase-dependent estrogen production, and chronic low-grade systemic inflammation. This review aimed to provide a systematic synthesis of current evidence regarding the mechanistic links between hyperprolactinemia and obesity, with an emphasis on the biological properties of prolactin, clinical characteristics of obesity complicated by HPRL, and molecular and physiological pathways underlying their reciprocal interactions. In addition, we critically evaluate current clinical management strategies, including dopamine agonist therapy and lifestyle-based weight-loss interventions, highlighting existing uncertainties and future directions aimed at improving the diagnosis and integrated management of these frequently coexisting conditions.