Maternal diet enrichment in n-3 long-chain polyunsaturated fatty acids during pregnancy and lactation improves their transfer from the mother to the offspring and counterbalances high-fat diet-induced alterations in a sex-dependent manner in rats

Background Low birth weight (LBW) increases the risk of developing metabolic disorders in adulthood and reduces fatty acid (FA) brain accretion in offspring in rodent models. As milk composition is partially influenced by maternal diet, it is conceivable to act on maternal diet to improve FA brain accretion and development in offspring. Methods We investigated the influence of n-3 long-chain polyunsaturated FA (LCPUFA) deficient and enriched maternal diets as well as high-fat diet challenge on key aspects of offspring development, including birth weight, milk and brain FA composition, glucose and lipids metabolism outcomes, and general behavior in male and female offspring from a rat model of maternal protein restriction. Results Maternal n-3 LCPUFA deficient diet leads to discernible alterations both in mother red blood cell (RBC) membranes, milk and offspring brain, impacting critical FA such as alpha-linolenic acid, eicosapentanoic acid (EPA), and docosahexanoic acid (DHA). The exact opposite effect is observed with a maternal EPA-, DHA-, and arachidonic acid (AA)-enriched diet. DHA, n-3 LCPUFA and the n-6/n-3 ratio in mother RBC membrane are identified as offspring predicting brain FA composition. N-3 deficient maternal diet clearly impacts metabolic health, in particular hepatic lipid metabolism, and general motor activity of the offspring later in life in a sex-dependent manner. Providing an EPA-DHA-AA enriched diet during gestation and lactation partially normalized these parameters. Conclusion Our findings demonstrate that maternal n-3 LCPUFA deficiency disrupts offspring brain FA composition and metabolic health, while an EPA-DHA-AA enriched diet during gestation and lactation partially restores these alterations, highlighting the potential of maternal dietary intervention to mitigate long-term developmental and metabolic risks in LBW offspring in particular after HFD challenge.