Human
milk is naturally rich in medium- and long-chain
triacylglycerols
(MLCT), accounting for approximately 30% of the total fat. However,
infant formula fat is prepared using a physical blend of vegetable
oils, which rarely contains MLCT, similar to human milk. The differences
in MLCT between human milk and infant formulas may cause different
lipid metabolisms and physiological effects on infants, which are
unknown. This study aimed to analyze the metabolic characteristics
of formula lipid containing novel human milk fat substitutes based
on MLCT (FL-MLCT) and compare their effects with those of the physical
blend of vegetable oils (FL-PB) on lipid metabolism and gut microbiota
in mice. Compared with the FL-PB group, the FL-MLCT group showed increased
energy expenditure, decreased serum triacylglycerol level, and significantly
lower aspartate aminotransferase level, epididymal and perirenal fat
weight, and adipocyte size. Moreover, the abundances of Firmicutes/Bacteroidota, Actinobacteriota, and Desulfovibrionaceae were significantly decreased
in the FL-MLCT group. Novel human milk fat substitutes MLCT could
inhibit visceral fat accumulation, improve liver function, and modulate
the mice gut microbiota composition, which may contribute to controlling
obesity.