Abstract
Background: Obesity is a multifactorial metabolic disorder influenced not only by excessive caloric intake but also by micronutrient imbalances such as zinc deficiency. Emerging evidence suggests that zinc regulates microRNA (miRNA) biogenesis and expression, linking nutritional status to metabolic regulation. Objective: This review delineates the molecular interplay between zinc and miRNAs in obesity, emphasizing the mechanistic, clinical, and translational relevance of zinc-sensitive miRNAs in adipogenesis, insulin resistance, inflammation, and oxidative stress. Results: Zinc deficiency alters miRNA expression profiles associated with metabolic dysregulation. Key miRNAs-miR-21, miR-34a, miR-122, and miR-144-3p-are consistently modulated by zinc status, influencing inflammation, lipid metabolism, and insulin signaling. Zinc repletion restores several miRNAs (e.g., miR-10b, miR-155, miR-145), suggesting reversibility, while excessive zinc may upregulate miR-144-3p and exacerbate oxidative stress. Circulating and exosomal miRNAs show promise as dynamic biomarkers for zinc intervention efficacy. Methods: A literature search was performed in 4 databases up to August 2025 using keywords related to zinc, miRNAs, and obesity. Eligible studies included both preclinical and human research evaluating zinc status or supplementation and miRNA expression in metabolic contexts. Conclusion: Maintaining optimal zinc levels may normalize miRNA expression and improve insulin sensitivity. The "zinc-miRNA axis" represents a novel frontier for precision nutrition in obesity management.