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. OBJECTIVES: The study aimed to evaluate the impact of n-3 long-chain polyunsaturated FA (LCPUFA) deficiency or enrichment in the maternal diet during gestation and lactation on maternal diet on milk composition, offspring brain lipids, and the potential to counterbalance the effects of a high-fat diet (HFD). METHODS: We investigated the influence of n-3 LCPUFA-deficient and -enriched maternal diets, as well as HFD challenge, on key aspects of offspring development, including birth weight, milk and brain FA composition, glucose and lipid 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 FAs such as α-linolenic acid, eicosapentaenoic acid (EPA), and docosahexaenoic 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 maternal RBC membrane are identified as offspring-predicting brain FA composition. An 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. CONCLUSIONS: Our findings demonstrate that maternal n-3 LCPUFA deficiency disrupts offspring brain FA composition and metabolic health, whereas 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.