Multi-omic analysis reveals that the CARNS1-mediated carnosine synthesis pathway modulates muscle metabolic responses...

Seasonal feed shortages pose critical challenges to ruminant productivity, yet the mechanisms underlying muscle metabolic responses to varying degrees of restriction remain unclear. This study simulated feed shortage in goats using three dietary treatments: normal feeding (RF0), 25% restricted feeding (RF25), and 50% restricted feeding (RF50). A total of 30 male Xiangdong black goats with similar initial body weight (19.14 ± 2.75 kg) and age (4.0 ± 0.3 months) were randomly assigned into 3 groups (n = 10 per group) for an 87-d trial (7-d preliminary period followed by an 80-d experimental period). By integrating growth performance, muscle morphology, fatty acid and free amino acid profiles, and transcriptomic and metabolomic data, the multilevel responses of goat muscle to feed shortage were characterized. As anticipated, restricted feeding markedly impaired growth performance; in particular, the average daily gain in the RF50 group decreased markedly compared with the RF0 group (P < 0.05). Morphological analysis revealed that RF50 significantly reduced the cross-sectional area of longissimus lumborum muscle fiber (P = 0.017) without affecting fiber diameter or density (P > 0.05) compared with the RF0 group, suggesting that structural preservation of fiber number was prioritized over individual fiber volume under severe nutritional stress. Metabolically, RF50 induced accumulation of free amino acids (aspartate, glycine, valine, and lysine) and monounsaturated fatty acids (cis9-C16:1n-7 and cis9-C18:1 n-9), and depletion of polyunsaturated fatty acids (cis9,cis12-C18:2n-6 and cis9,cis12,cis15-C18:3n-3) compared with the RF0 group (P < 0.05). Transcriptomic analysis revealed suppression of protein processing in the endoplasmic reticulum, beta-alanine metabolism, PPAR signaling pathway, aminoacyl-tRNA biosynthesis, fatty acid metabolism, and fatty acid degradation pathways under RF50 (P-adjust < 0.05); concordant downregulation of the beta-alanine metabolism and aminoacyl-tRNA biosynthesis pathways was also observed in the metabolome. Trend clustering identified a nonlinear metabolic threshold, with RF25 inducing gradual adaptations while RF50 triggered abrupt metabolic reprogramming. Integrated multiomics analysis identified the beta-alanine metabolism pathway as a pivotal hub, marked by coordinated downregulation of CARNS1 and significantly reduced levels of carnosine and L-histidine in the RF50 group (P-adjust < 0.05). These findings suggest that severely restricted feeding disrupts muscle homeostasis via the CARNS1-mediated carnosine synthesis pathway, impairing fatty acid metabolism and protein turnover. The adverse effects of RF50 on muscle characteristics were more pronounced than those of RF25, indicating that maintaining feed intake at a minimum of 75% during seasonal feed shortages may prevent irreversible muscle damage and mitigate nutritional stress in goats.