Liver miRNome is modulated by nutrient restriction in early lactation cows challenged with intramammary lipopolysaccharide.

Dairy cows are vulnerable to health problems during the transition period, associated with a negative energy balance (NEB). MicroRNAs are known to influence many biological processes including inflammation. This study aimed to evaluate the effects of nutrient restriction on liver miRNome 24 h after an intramammary lipopolysaccharide (LPS) challenge in early-lactation Holstein cows. Cows were assigned to constant lactation diet throughout the study (CONT) or were switched to a diet diluted with barley straw for 96 h (REST) starting at 24 ± 3 days in milk. In all cows, mammary inflammation was induced at 72 h by an intramammary injection of 50 μg of LPS. Blood, milk and liver biopsies were collected at 24 h post-LPS challenge and thus at 96h after nutrient restriction. In the REST group, plasma concentrations of non-esterified fatty acids (NEFA) and β-hydroxybutyrate (BHB) increased. In liver, 615 known miRNAs were identified by small RNA-Sequencing. Among them, 23 miRNAs were highly expressed (>100,000 reads), representing over 91 % of total reads. We identified two miRNAs (miR-143 and let-7f) consistently abundant across cattle breeds, suggesting conserved roles in liver function. Nutrient restriction altered the expression of five miRNAs (miR-30e-5p, miR-33a-5p, miR-33b-5p, miR-100-5p and miR-210-3p), with miR-30e-5p being one of the most abundant in bovine liver. These miRNAs were correlated with milk production and composition, plasma NEFA and BHB concentrations. Functional predictions suggest that these miRNAs may regulate biological processes related to cellular processes, nucleic acid metabolism, protein processing, and metabolic and lipid processes. Three of these miRNAs (miR-30e-5p, miR-100 and miR-210) were reported to be potentially involved in immune responses.