Glutamine relieves feed restriction-induced ruminal epithelial function damage through histone lysine lactylation in yaks.

BACKGROUND: As a unique livestock adapted to the harsh environment, grazing yaks frequently suffer from malnutrition and even death because of the lower yield and quality of forage in the Qinghai-Tibet Plateau during the cold season. Certain stress conditions, such as environmental changes, disease, and malnutrition, can lead to a decrease in glutamine (Gln) synthesis, which fails to cover the physiological needs of the organism. Supplementation with exogenous Gln can promote nutrient digestion and improve rumen fermentation in ruminant animals under malnutrition. However, whether Gln could alleviate the barrier function injury induced by malnutrition and its mechanism is still unclear. METHODS: In the in vivo experiments, 24 healthy yaks (31 months, 265.35 ± 25.81 kg) were randomly divided into 3 groups, namely control group (Con, free access to the basal diet), feed restriction group (FR, 50% level of ad libitum feed intake), and feed restriction + Gln group (FR + Gln, 50% level of ad libitum feed intake from d 1 to 30, 50% level of ad libitum feed intake + 1% Gln from d 31 to 60). In the in vitro experiments, the yak rumen epithelial cells (YRECs) were divided into 4 groups: Con group (complete medium), Gln group (complete medium + 10 mmol/L Gln), Gln deficiency group (Gln-D, Gln-free medium), and Gln deficiency + Gln group (Gln-D + Gln, Gln-free medium + 10 mmol/L Gln). RESULTS: In the in vivo experiments, FR significantly decreased the ruminal concentrations of acetate, propionate, butyrate, iso-butyrate, and total volatile fatty acid (VFA) (P < 0.05). FR also reduced the mRNA expression of NHE1, Na(+)/K(+)-ATPase, and Ca(2+)/Mg(2+)-ATPase, and the concentrations of lactate, histone acetyltransferase (p300), histone deacetylase (HDAC), as well as the histone lysine lactylation level compared to Con group, while Gln supplementation alleviated them (P < 0.05). In the in vitro experiments, Gln alleviated the Gln-D-induced down-regulation of NHE1, Na(+)/K(+)-ATPase, and Ca(2+)/Mg(2+)-ATPase mRNA expressions and reduction of lactate, p300, HDAC concentrations, and histone lysine lactylation level (P < 0.05). Besides, p300 inhibitor abrogated Gln repair of barrier function damage in YRECs (P < 0.05). CONCLUSIONS: Overall, our results revealed the potential mechanism of Gln supplementation to repair malnutrition-induced damage of rumen epithelial barrier function in yaks, which might be related to histone lysine lactylation. However, because we do not have a control group receiving glutamine alone, we cannot determine the impact of Gln on the rumen epithelial function of normal yaks.