Coated cobalamin alleviates heat stress in lactating Holstein cows by enhancing ruminal propionate production, antioxidant capacity, and hepatic mitogen-activated protein kinase signaling

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BACKGROUND: Heat stress compromises dairy cow productivity and metabolic health through impaired nutrient partitioning and oxidative stress. Cobalamin is an essential cofactor for methylmalonyl-CoA mutase, the key enzyme regulating ruminal propionate production and hepatic gluconeogenic metabolism. However, the underlying molecular mechanisms, particularly the hepatic transcriptional responses to cobalamin under heat stress conditions, remain unclear. This study evaluated the effects of coated cobalamin (CCA) supplementation on lactation performance, nutrient digestibility, rumen fermentation, blood metabolites, and hepatic transcriptome in heat-stressed Holstein cows. RESULTS: Forty Holstein cows (2.25 ± 0.07 parity; 105 ± 10.4 DIM; 41.5 ± 6.83 kg/d milk yield) were assigned to two groups (n = 20) in a randomized block design: (1) control (CON; without CCA) or (2) CCA (addition of CCA at 6 g/d). The experimental period was 64 days, during which the mean temperature-humidity index was 77.1 ± 2.49 (mean ± SD). Respiratory rate was lower in CCA-fed cows than in CON cows. Nutrient intake did not differ, whereas fat-corrected milk, milk protein yields, and feed efficiency were greater for cows receiving CCA. Supplementation with CCA increased ruminal total volatile fatty acid concentration and propionate proportion, but decreased acetate-to-propionate ratio. Apparent digestibilities of organic matter and neutral detergent fiber were greater in the CCA group compared with the CON. Plasma glutathione peroxidase, total antioxidant capacity, and cobalamin were greater, but tumor necrosis factor-α and interleukin-1β were lower for cows in the CCA group. Liver transcriptome analysis revealed that mitogen-activated protein kinase (MAPK), phagosome, and peroxisome proliferator-activated receptor (PPAR) signaling pathways, along with the JUN, FOS, and GADD45G gene family, were key pathways and genes through which CCA regulated hepatic metabolism in heat-stressed cows. CONCLUSION: Coated cobalamin addition alleviates heat stress, and increases lactation performance, rumen propionate production, and antioxidant status in dairy cows. Hepatic MAPK signaling pathway mediated the metabolic benefits of CCA in heat-stressed dairy cows. These findings support CCA supplementation as a practical nutritional strategy for mitigating heat stress and provide a mechanistic basis for understanding how targeted nutrient delivery modulates systemic metabolism through hepatic transcriptional regulation.

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