Guanidinoacetic Acid and Methionine Supplementation Improve the Growth Performance of Beef Cattle via Regulating the Antioxidant Levels and Protein and Lipid Metabolisms in Serum and Liver

Guanidinoacetic acid (GAA) has been used in ruminant feeding, but it is still unclear whether the exogenous addition of methyl donors, such as methionine (Met), can enhance the effects of GAA. This study investigated the effects of dietary GAA alone or combined with Met on beef cattle growth performance and explored the underlying mechanisms via blood analysis, liver metabolomics, and transcriptomics. Forty-five Simmental bulls (453.43 ± 29.05 kg) were assigned to three groups for 140 days: CON (control), GAA (0.1% GAA), and GAM (0.1% GAA + 0.1% Met), where each group consisted of 15 bulls. Compared with the CON group, the average daily gain (ADG) and feed conversion efficiency (FCE) of the two feed additive groups were significantly increased, and the digestibility of neutral detergent fiber (NDF) was improved (<i>p</i> < 0.05). Among the three treatment groups, the GAM group showed a higher rumen total volatile fatty acids (TVFAs) content and digestibility of dry matter (DM) and crude protein (CP) in the beef cattle. The serum indices showed that the contents of indicators related to protein metabolism, lipid metabolism, and creatine metabolism showed different increases in the additive groups (<i>p</i> < 0.05). It is worth noting that the antioxidant indexes in the serum and liver tissues of beef cattle in the two additive groups were significantly improved (<i>p</i> < 0.05). The liver metabolites related to protein metabolism (e.g., L-asparagine, L-glutamic acid) and lipid metabolism (e.g., PC (17:0/0:0)) were elevated in two additive groups, where Met further enhanced the amino acid metabolism in GAM. In the two additive groups, transcriptomic profiling identified significant changes in the expression of genes associated with protein metabolism (including <i>PIK3CD</i>, <i>AKT3</i>, <i>EIF4E</i>, <i>HDC</i>, and <i>SDS</i>) and lipid metabolism (such as <i>CD36</i>, <i>SCD5</i>, <i>ABCA1</i>, <i>APOC2</i>, <i>GPD2</i>, and <i>LPCAT2</i>) in the hepatic tissues of cattle (<i>p</i> < 0.05). Overall, the GAA and Met supplementation enhanced the growth performance by improving the nutrient digestibility, serum protein and creatine metabolisms, antioxidant capacity, and hepatic energy and protein and lipid metabolisms. The inclusion of Met in the diet was shown to enhance the nutrient digestibility and promote more efficient amino acid metabolism within the liver of the beef cattle.