Dietary Capsiate-Producing Chili Pepper Promotes Somatic and Femoral Growth and Modulates Intestinal Immunometabolic Responses in Mice

Capsaicin has been investigated as a phytogenic feed additive in animal production due to reported growth-promoting and immunomodulatory properties; however, its pungency limits practical application. Capsiate, a naturally occurring non-pungent capsaicin analog present in specific Capsicum annuum accessions, conserves many of its bioactive properties without inducing sensory irritation and has not been studied as a potential growth-promoting alternative. The present study evaluated whether dietary exposure to a capsiate-producing chili pepper influences growth and assessed associated intestinal responses using a murine model. A capsiate-producing Capsicum annuum accession (509-45-1) was characterized and incorporated into experimental diets providing 30 or 50 mg/kg capsiate to male C57BL/6J mice for 12 weeks. The dietary intervention was associated with dose-dependent increases in body weight and longitudinal femoral growth without altering body composition. Femoral elongation was accompanied by increased growth plate area and higher osteocyte number and area. At the intestinal level, the intervention was associated with downregulation of colonic transient receptor potential vanilloid 1 (TRPV1) gene expression, modulation of redox-associated responses, including catalase (CAT) and superoxide dismutase (SOD) expression, and differential modulation of innate immune signaling, including upregulation of Toll-like receptor 2 (TLR2) and downregulation of Toll-like receptor 4 (TLR4), together with reduced interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) expression. Collectively, these findings indicate that dietary supplementation with a capsiate-producing chili is associated with increased somatic growth and enhanced femoral development in mice, accompanied by intestinal transcriptional changes consistent with immunometabolic responses, while preserving body composition.