Enhanced lactose utilization from milk enriched in Uridine-5'-monophosphate drives hepatic energy storage in young mammals.

Lactose is the primary carbohydrate in milk, but its role in neonatal metabolic adaptation remains unclear. This study aimed to clarify the correlation between milk pyrimidine nucleotides and hepatic energy metabolism during lactose metabolism via three animal models. A sow-piglet model characterized natural milk nucleotide dynamics and their correlation with hepatic metabolism in suckling piglets. An ultra-early weaned piglet model evaluated uridine monophosphate (UMP) supplementation under controlled high-lactose conditions. A high-lactose rat model validated conserved metabolic alterations. Natural lactation analysis revealed that milk lactose increased obviously at days 7, 14 and 21 relative to colostrum, while milk pyrimidine nucleotides decreased gradually. Accordingly, suckling piglets exhibited increased serum triglyceride and decreased hepatic glycogen, together with suppressed expression of hepatic pyrimidine synthesis-related genes at later lactation stages. On this basis, we further explored the effects of UMP supplementation using high-lactose-fed piglets and rats. Dietary UMP supplementation was associated with increased hepatic glycogen and triglyceride accumulation in both species. UMP intervention coincided with increased activities of gluconeogenic and Leloir pathway enzymes, as well as altered expression of lipogenic genes. These changes were accompanied by changes in AMPK/mTOR, PPARγ and IL-6 signaling. Collectively, these results suggest that UMP supplementation was associated with hepatic energy storage in young mammals fed a lactose-containing diet.