Integrated transcriptomics and metabolomics reveal suppression of the PPAR α/γ pathway linking purine metabolism disorder to high-protein diet-induced hyperuricemia in goslings.

Hyperuricemia (HUA) and gout in goslings are increasingly recognized in intensive production systems, yet liver involvement in HUA remains poorly understood. This study examines how a high-protein diet influences gosling HUA through liver transcriptional and metabolic alterations. In Exp. Ⅰ, a total of 80 one-d-old male goslings (93.13 ± 0.96 g) were randomly assigned to four dietary treatments containing 18% (control group), 21% (P21 group), 24% (P24 group), and 27% (P27 group) crude protein (CP), with four replicates of five birds per treatment, for an 18-d experimental period to establish a HUA model. Goslings fed the 24% CP diet exhibited joint swelling, sparse plumage, and white feces, accompanied by reduced average daily gain (ADG; P = 0.011) and average daily feed intake (ADFI; P < 0.001). Serum uric acid (P = 0.005), xanthine oxidase (XOD; P = 0.009), xanthine dehydrogenase (XDH; P = 0.018), aspartate aminotransferase (AST; P < 0.001), urea (P < 0.001), interleukin-1β (IL-1β; P = 0.010), and tumor necrosis factor-α (TNF-α; P < 0.001) levels were significantly elevated in the P24 group, consistent with HUA-associated metabolic and inflammatory alterations. In Exp. Ⅱ, a total of 40 one-d-old goslings (93.88 + 0.92 g) were randomly assigned to two groups (n = 20 per group) and fed an 18% CP basal diet (CON group) or a 24% CP diet (HUA group) for 18 d. The HUA group showed increased liver index (P = 0.001), hydropic and partial lipid degeneration, hepatocyte swelling, and marked mitochondrial swelling observed by transmission electron microscopy (TEM). Integrated transcriptomics and metabolomics of the liver revealed that decreased levels of 9-hydroxyoctadecadienoic acid (9-HODE) and 8(S)-hydroxyeicosatetraenoic acid [8(S)-HETE] were associated with suppression of the peroxisome proliferator-activated receptor α/γ (PPARα/γ) signaling pathway. Meanwhile, the upregulation of ACSL6 and ACSBG2 was linked to a 2.61-fold increase in adenosine monophosphate (AMP) accumulation. Elevated AMPD3 and NT5C1B expression enhanced AMP-to-inosine conversion (1.69-fold), and coordinated up-regulation of NT5C1B, PNP, and XDH further accelerated UA formation in purine metabolism, collectively contributing to HUA and associated inflammatory responses. Although graded increases in dietary CP induced proportional shifts in digestible amino acid concentrations, these results reveal a strong correlation between high-protein diets and HUA, as well as subsequent liver and renal injuries in goslings.