Lipocalin 2—A bone‐derived anorexigenic and β‐cell promoting signal: From mice to humans

The skeleton is traditionally known for its structural support, organ protection, movement, and maintenance of mineral homeostasis. Over the last 10 years, bone has emerged as an endocrine organ with diverse physiological functions. The two key molecules in this context are fibroblast growth factor 23 (FGF23), secreted by osteocytes, and osteocalcin, a hormone produced by osteoblasts. FGF23 affects mineral homeostasis through its actions on the kidneys, and osteocalcin has beneficial effects in improving glucose homeostasis, muscle function, brain development, cognition, and male fertility. In addition, another osteoblast‐derived hormone, lipocalin 2 (LCN2) has emerged into the researchers' field of vision. In this review, we mainly focus on LCN2's role in appetite regulation and glucose metabolism and also briefly introduce its effects in other pathophysiological conditions, such as nonalcoholic fatty liver disease, sarcopenic obesity, and cancer‐induced cachexia. Highlights Lipocalin 2 (LCN2) suppresses appetite through melanocortin‐4 receptor. LCN2 protects β‐cell from damage and enhance their proliferation. LCN2 orchestrates energy metabolism by maintaining homeostasis of lipid metabolism in liver and supporting muscle regeneration. Targeting LCN2 holds significant therapeutic potential for managing both metabolic disorders and cachexia.