Integrated multi-omics analyses reveal impaired energy homeostasis underlying tongue-rolling behavior in dairy cattle.

Tongue rolling in cattle is a stereotypic behavior with poorly understood biological basis. Here, we show that it is not associated with alterations in blood mineral status, but is characterized by significantly reduced serum glucose, indicating impaired energy homeostasis. Multi-omics analyses revealed coordinated molecular changes, with transcriptomic enrichment in Rap1 and Ras signaling pathways and proteomic enrichment in lipid metabolism and energy-related processes. Key regulators of glucose homeostasis (RAP1A/B) and fatty acid oxidation (e.g., MCAD) were upregulated, suggesting adaptive metabolic reprogramming. Despite activation of compensatory pathways, reduced glucose availability persisted. These findings indicate that tongue rolling represents a metabolic phenotype driven by chronic energy imbalance and dysregulated energy-sensing pathways, rather than a consequence of isolated nutritional deficiency.