Investigating the Short-Term Effects of Cold Stress on Metabolite Responses and Metabolic Pathways in Inner-Mongolia Sanhe Cattle

Simple Summary Cold stress is a major environmental stressor affecting cattle performance in temperate regions, which causes impaired welfare and economic losses to cattle producers. The identification of biological mechanisms associated with cold stress response is paramount for developing effective mitigation strategies, such as genomic selection. In this study, we assessed the short-term effects of hyper-cold stress on metabolite responses and metabolic pathways in the serum of Inner-Mongolia Sanhe cattle. Moreover, 19 differential metabolites were found, mainly involved in amino acid metabolism. A further integration of metabolome results and gene expression highlighted the regulation of metabolic changes and related pathways in severe cold exposure, such as "aminoacyl-tRNA biosynthesis" and "valine, leucine, and isoleucine degradation". In summary, we presented new insights on the short-term effects of severe cold stress as well as metabolites and metabolic pathways associated with cold stress response in Inner-Mongolia Sanhe cattle. Inner-Mongolia Sanhe cattle are well-adapted to low-temperature conditions, but the metabolic mechanisms underlying their climatic resilience are still unknown. Based on the H-1 Nuclear Magnetic Resonance platform, 41 metabolites were identified and quantified in the serum of 10 heifers under thermal neutrality (5 degrees C), and subsequent exposure to hyper-cold temperature (-32 degrees C) for 3 h. Subsequently, 28 metabolites were pre-filtrated, and they provided better performance in multivariate analysis than that of using 41 metabolites. This indicated the need for pre-filtering of the metabolome data in a paired experimental design. In response to the cold exposure challenge, 19 metabolites associated with cold stress response were identified, mainly enriched in "aminoacyl-tRNA biosynthesis" and "valine, leucine, and isoleucine degradation". A further integration of metabolome and gene expression highlighted the functional roles of the DLD (dihydrolipoamide dehydrogenase), WARS (tryptophanyl-tRNA synthetase), and RARS (arginyl-tRNA synthetase) genes in metabolic pathways of valine and leucine. Furthermore, the essential regulations of SLC30A6 (solute carrier family 30 (zinc transporter), member 6) in metabolic transportation for propionate, acetate, valine, and leucine under severe cold exposure were observed. Our findings presented a comprehensive characterization of the serum metabolome of Inner-Mongolia Sanhe cattle, and contributed to a better understanding of the crucial roles of regulations in metabolites and metabolic pathways during cold stress events in cattle.