State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
Redox Biol. 2023 Nov;67:102889. doi: 10.1016/j.redox.2023.102889. Epub 2023 Sep 19.
Maternal diets during pregnancy and lactation are key determinants that regulate the development of metabolic syndrome (MetS) in offspring. l-malic acid (MA) was previously reported to improve antioxidant capacity and aerobic metabolism. However, the effects of maternal MA consumption on the metabolic features of offspring remain largely unexplored. Herein, through pig models consuming MA-enriched diets during late pregnancy and lactation, we found that maternal MA consumption potentiated the anti-inflammatory and antioxidant capacity of sows, thereby improving their reproductive performance and the growth performance of piglets. Maternal MA consumption also induced a transition of slow-twitch to fast-twitch fibers in the early life of offspring. Along with muscle growth and fiber-type transition, insulin sensitivity and glucose metabolism, including aerobic metabolism and glycolysis, were improved in the skeletal muscle of offspring. An untargeted metabolomic analysis further revealed the contribution of modified amino acid metabolism to the improved aerobic metabolism. Mechanistically, maternal MA consumption remodeled colonic microbiota of their offspring. Briefly, the abundance of Colidextribacter, Romboutsia, and Family_XIII_AD3011_group increased, which were positively associated with the antioxidant capacity and glucose metabolism of skeletal muscles. A decreased abundance of Prevotella, Blautia, Prevotellaceae_NK3B31_group, and Collinsella was also detected, which were involved in less insulin sensitivity. Notably, milk metabolites, such as ascorbic acid (AA) and granisetron (GS), were found as key effectors regulating the gut microbiota composition of piglets. The properties of AA and GS in alleviating insulin resistance, inflammation, and oxidative stress were further verified through mice treated with high-fat diets. Overall, this study revealed that maternal MA consumption could modulate the inflammatory response, antioxidant capacity, and glucose metabolism by regulating the gut microbiota of offspring through the vertical transmission of milk metabolites. These findings suggest the potential of MA in the prevention and treatment of MetS in early life.
母体在妊娠和哺乳期的饮食是调节后代代谢综合征（MetS）发展的关键决定因素。L-苹果酸（MA）先前被报道能提高抗氧化能力和有氧代谢。然而，母体 MA 消耗对后代代谢特征的影响在很大程度上仍未得到探索。在此，通过妊娠晚期和哺乳期摄入 MA 丰富饮食的猪模型，我们发现母体 MA 消耗增强了母猪的抗炎和抗氧化能力，从而提高了它们的繁殖性能和仔猪的生长性能。母体 MA 消耗还诱导了后代生命早期慢肌向快肌纤维的转变。伴随着肌肉生长和纤维类型的转变，后代骨骼肌中的胰岛素敏感性和葡萄糖代谢，包括有氧代谢和糖酵解，得到了改善。非靶向代谢组学分析进一步揭示了氨基酸代谢的改变对有氧代谢的改善作用。在机制上，母体 MA 消耗重塑了后代的结肠微生物群。简而言之，Colidextribacter、Romboutsia 和 Family_XIII_AD3011_group 的丰度增加，这与骨骼肌的抗氧化能力和葡萄糖代谢呈正相关。还检测到Prevotella、Blautia、Prevotellaceae_NK3B31_group 和 Collinsella 的丰度降低，这与胰岛素敏感性降低有关。值得注意的是，发现了如抗坏血酸（AA）和格拉司琼（GS）等乳代谢物，作为调节仔猪肠道微生物群组成的关键效应物。通过用高脂肪饮食处理的小鼠进一步验证了 AA 和 GS 在缓解胰岛素抵抗、炎症和氧化应激方面的特性。总的来说，这项研究表明，母体 MA 消耗可以通过调节乳代谢物的垂直传递来调节后代的炎症反应、抗氧化能力和葡萄糖代谢，从而调节后代的肠道微生物群。这些发现表明 MA 在预防和治疗生命早期 MetS 方面具有潜力。
