Adipocyte-derived apelin protects against radiation-induced enteropathy through Wnt/β-catenin–mediated intestinal regeneration

Radiation-induced enteropathy is a progressive and debilitating condition resulting from abdominal or pelvic radiotherapy, nuclear accidents, or radiological terrorism. Interaction between the intestine and mesenteric adipose tissue (MAT) is a key factor in intestinal homeostasis, but the molecular crosstalk involved remains poorly understood. We investigated the roles of MAT and adipokine apelin in protection against radiation-induced intestinal injury. Here, we identified that radiation exposure led to a marked reduction in adipogenesis and dysregulation of adipokine expression. Mice lacking MAT exhibited exacerbated epithelial damage, increased inflammation, and impaired regenerative capacity. Among the adipokines identified, apelin was significantly diminished in irradiated MAT. Apelin administration effectively preserved intestinal architecture, reduced inflammatory cell infiltration, and restored epithelial barrier function. Apelin pretreatment-but not post-treatment-maintained intestinal stem cell marker expression and activated Wnt/β-catenin signalling. MAT is a crucial modulator of intestinal radiation response. Apelin is an adipokine with radioprotective and radiomitigative properties and plays a role in stem cell protection and regeneration. These results advance our understanding of adipose-intestinal crosstalk and suggest apelin as a therapeutic candidate for managing radiation-induced gastrointestinal toxicity.