Adropin-Driven Browning: Targeting M2 Macrophages to Combat PCOS

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age, associated with chronic low-grade inflammation and metabolic disorders. The exact pathogenesis of PCOS remains unclear. Adropin, a secreted protein encoded by the energy homeostasis gene (Enho), has immunometabolic regulatory functions. In the present study, the serum levels of adropin were significantly lower (P < 0.001) in PCOS mice than controls, and adropin deficiency exacerbated the obesity and inflammatory phenotypes in letrozole (LTZ)-induced PCOS mice. In vitro experiments, it has shown that adropin mediated the phenotypic change of RAW264.7 macrophages to M2 through upregulation of heme oxygenase-1 (HO-1), and then adropin-treated macrophage-conditioned medium (Adr-CM) induced browning of fully differentiated 3T3-L1 adipocytes. Finally, vivo experiments by injecting adropin into PCOS model mice showed that adropin treatment significantly reduced body weight, and promoted macrophage M2 anti-inflammatory phenotypic transformation and browning of white adipose tissue. In summary, the present study reveals a novel mechanism by which adropin indirectly promotes adipose tissue browning by regulating macrophage polarisation, which provides a new perspective and experimental basis for the therapeutic strategy of PCOS and its related metabolic disorders.