Current Understanding of Bovine Ketosis: From Molecular Basis to Farm-Level Management.

Bovine ketosis represents a critical metabolic challenge in modern dairy production, primarily affecting high-yielding cows during the periparturient period. The disorder arises from severe negative energy balance (NEB), where energy demands exceed supply, triggering substantial mobilization of adipose tissue and hepatic accumulation of non-esterified fatty acids (NEFAs). This stress overwhelms hepatic oxidative capacity, leading to incomplete fatty acid oxidation and excessive ketone body production-primarily β-hydroxybutyrate (BHB), acetoacetate, and acetone. While genomics enables the identification of candidate genes and genetic variations influencing ketosis susceptibility, metabolomics provides comprehensive, multi-matrix metabolic signatures across blood, milk, urine, and tissues, often revealing predictive biomarkers in the dry period and pre-clinical stage. This review provides a comprehensive overview of ketosis etiology, emphasizing the roles of NEB, fat mobilization, hormonal dysregulation, and oxidative stress. We systematically examine candidate genes, signaling pathways, and the diverse metabolomic profiles underlying disease pathogenesis, and discuss current prevention strategies focusing on periparturient nutritional management and therapeutic interventions. Understanding these integrated molecular and metabolic mechanisms offers valuable insights for developing targeted breeding programs and precision management approaches to enhance metabolic health and economic efficiency in dairy cattle.