Alterations in Methionine Cycle and Wnt/MAPK Signaling Associated with HMBi-Induced Cashmere Growth in Goats

Methionine (Met) was the first limiting amino acid identified in cashmere goats, and 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester (HMBi) can effectively provide Met and encourage cashmere growth in goats. However, existing studies have primarily centered on the trait of cashmere growth and have not delved into the underlying molecular and physiological mechanisms by which HMBi promotes cashmere growth in goats. In the present study, we combined metabolomic and transcriptomic approaches to reveal the effects of HMBi supplementation and its impact on the gene expressions and metabolic profiles within the skin tissue of Liaoning cashmere goats. A total of 14 female Liaoning cashmere goats were randomly allocated to the control (CON) and HMBi groups. The CON group received a basal diet, and the HMBi group was fed the basal diet plus 1.27% HMBi. Our results show that HMBi supplementation significantly increased (<i>p</i> < 0.05) the cashmere length and decreased the cashmere diameter in the goats. The metabolomics results show that the HMBi supplementation increased (variable importance in projection >1 and <i>p</i> < 0.05) the concentrations of Met, 2-Hydroxy-4-methylthiobutanoic acid (HMB), proline betaine, and 10-hydroxydecanoic acid in the skin tissue of the goats. For HMB degradation and Met cycle-related genes, compared with the CON diets, the HMBi diets elevated (<i>p</i> < 0.05) LDHD, MAT1A, and AHCY by 86.33%, 154.54%, and 147.89% in the skin tissue, respectively. Regarding genes related to cell proliferation and differentiation, the HMBi supplementation increased (<i>p</i> < 0.05) CCND1, CDK4, IVL, and BMP4 by 113.31%, 107.93%, 291.33%, and 186.21%, respectively. The results of the transcriptome evaluation show that the differential expression genes were mainly enriched (<i>p</i> < 0.05) in the Wnt and MAPK signaling pathways. In summary, these findings indicate that the Met cycle, Wnt, and MAPK play important roles in the process of HMBi, promoting cashmere growth in Liaoning cashmere goats.