**Background:** Farmers commonly use high-concentrate diets (HCDs) during ruminant fattening to improve growth performance and compensate for low-quality roughage. However, long-term HCD consumption can cause rumen microflora disorders and nutritional metabolic diseases such as subacute ruminal acidosis, laminitis, and liver abscess. While these effects are well-documented in cattle, sheep and goats appear more adaptable to HCDs, possibly due to higher rumen buffering capacity. The liver plays a critical role in metabolizing nutrients and detoxifying harmful substances absorbed from the gastrointestinal tract. This study aimed to determine the effects of HCD on blood parameters and liver transcriptome in goats.
**Methods:** Eighteen Jianzhou big ear goats (4 months old, 20.26 ± 2.63 kg) were randomly allocated into three groups (6 per group): HC (concentrate:roughage = 80:20), MC (50:50), and LC (25:75). After a 14-day adjustment period, the formal trial lasted 67 days (60-day feeding trial, 6-day digestion trial, and sampling). Blood samples were collected from the hepatic portal vein (HPV) and jugular vein (JV). Nutrient digestibility was measured. Liver, rumen, jejunum, and colon tissues were collected for histopathology and transcriptome sequencing. RNA-seq was performed on liver tissue, and DEGs were identified using |log2(fold change)| ≥ 1 and adjusted p-value < 0.05. Eight DEGs were validated by RT-qPCR.
**Key Results:** The HC group showed significantly higher digestibility of DM, CP, GE, NDF, and EE compared to LC and MC groups (p < 0.05). In HPV blood, HC had significantly higher LPS, VFAs, and LA concentrations (p < 0.05). In JV blood, no significant differences in LPS, VFAs, or LA were found among groups (p > 0.05). However, HC showed significantly increased IL-1β, IL-10, TNF-α, and DAO in JV blood (p < 0.05). Liver transcriptome analysis identified 1,119 DEGs across groups, with 333 up-regulated and 608 down-regulated in HC vs. LC. GO enrichment showed DEGs focused on triacylglycerol catabolism, lipoprotein particle remodeling, and cholesterol transport. KEGG analysis revealed activation of AMPK, PPAR, insulin, thermogenesis, NF-κB, and toll-like receptor signaling pathways in HC. Key genes including ACACA (fatty acid synthesis), ATP6, COX7A1, CPT1B (oxidative phosphorylation), and TLR4, TLR7 (LPS recognition) were up-regulated in HC. Jejunal tissue in HC showed significantly more injury and inflammatory cell infiltration (p < 0.05), while liver, rumen, and colon histopathology showed no significant differences among groups.
**Clinical Implications:** This study demonstrates that goats can adapt to short-term HCD feeding (67 days) through enhanced liver function—increasing nutrient metabolism via AMPK and thermogenesis pathways while upregulating LPS detoxification via toll-like receptor signaling. The liver effectively cleared LPS and VFAs before they reached systemic circulation, preventing hyperlipidemia and hyperglycemia. However, elevated inflammatory cytokines (IL-1β, TNF-α) and jejunal damage suggest that long-term HCD feeding may induce chronic inflammation and health problems. These findings support the rational short-term use of HCDs in goat production but caution against prolonged application without monitoring inflammatory markers.