Olympia Michalopoulou, Ifigenia Kostoglou‐Athanassiou, Georgios Troupis, George Mastorakos
Nowadays, adipose tissue is recognized as a dynamic endocrine organ that profoundly affects metabolic, reproductive and skeletal physiology. Apart from its role in energy storage, adipocytes secrete cytokines and bioactive proteins, known as adipokines, that contribute to the regulation of the hypothalamic-pituitary-gonadal axis, gonadal steroidogenesis and bone remodeling. Reciprocal signaling between adipose tissue, bone and the reproductive system forms a complex endocrine network linking energy balance to fertility and bone homeostasis. Key mediators, including leptin, adiponectin, resistin, visfatin and bone marrow adipose tissue, interact with osteoblast-derived proteins, such as osteocalcin, to modulate steroidogenesis and metabolic function. Vitamin D, stored in adipose tissue and acting through its receptor, further integrates these pathways by coordinating calcium metabolism, reproduction and skeletal integrity. This review aims to present mechanistic and clinical evidence demonstrating how metabolic signals derived from adipose depots communicate with gonadal and skeletal tissues through overlapping endocrine, paracrine and autocrine networks. Attention is paid to depot-specific effects, bidirectional feedback between adipose tissue and bone signaling, as well as in emerging implications for infertility, osteoporosis and metabolic bone disease. Finally, we discuss critical knowledge gaps and research priorities, to elucidate novel therapeutic approaches for reproductive and skeletal disorders.