Effects of Human Milk Fat Substitutes on Lipid Metabolism in First-Weaned Rats

Although numerous studies indicate that formula-fed infants are more prone to obesity than breastfed ones, the underlying reasons have not been fully elucidated. This study aimed to determine the impact of human milk fat substitutes (HMFS) on the lipid metabolism of first-weaned Sprague Dawley rats. The findings revealed that administering HMFS did not affect the body weight of the rats (control: 298.38 ± 26.73 g, OPO (1,3-dioleic acid-2-palmitoyl triglyceride): 287.82 ± 19.85 g and HMFS: 302.31 ± 19.21 g), but it significantly decreased their body fat content (control: 28.70 ± 1.17 cm3, OPO: 22.51 ± 1.10 cm3 and HMFS: 14.90 ± 0.95 cm3) (p < 0.05). Lipidome analysis revealed that glycerophospholipid was the primary differentiating lipid present in the liver of HMFS-fed rats. The abundance of Bacteroides significantly increased in the intestine of HMFS-fed rats (p < 0.05), and their short-chain fatty acid (SCFA) content significantly increased (p < 0.05). The multi-omics correlation analysis established the “Bacteroidetes-SCFAs-Glycerophospholipid pathway” as a potential mechanism by which administering HMFS affects body fat buildup in first-weaned rats. Additionally, it was found that HMFS administration significantly promoted lipid metabolism in the rat liver at both the gene and protein levels (p < 0.05). These findings serve to underscore the nutritional benefits of HMFS for infants.