Kolling Institute of Medical Research, St Leonards, NSW 2065, Australia.
North Precinct, Sydney Medical School, University of Sydney, Sydney, NSW 2065, Australia.
Nutrients. 2023 Dec 28;16(1):109. doi: 10.3390/nu16010109.
Early-life exposure to maternal obesity predisposes offspring to metabolic-associated fatty liver disease (MAFLD). This study aimed to determine if peripartum weight loss, either through dietary intervention or pharmacological intervention, improved adverse liver health outcomes in the offspring of mothers with obesity. C57Bl/6 dams were fed a chow diet or a high-fat diet (HFD) for 8 weeks. HFD-fed mice either continued HFD, transitioned to a chow diet, or were administered liraglutide for 4 weeks. Pregnancy was induced following a one-week washout of liraglutide during which all animals remained on their respective diets. A proportion of HFD-fed mice transitioned to a chow diet during pregnancy. All offspring were weaned to the HFD. Offspring anthropometric, metabolic, and hepatic outcomes were assessed at postnatal week 12. The offspring of mothers with obesity had phenotypic changes consistent with MAFLD. The offspring of mothers that had weight loss with perinatal dietary intervention had reduced insulin resistance ( < 0.001) and hepatic expression of markers of inflammation ( < 0.001), oxidative stress ( < 0.05), and fibrosis ( < 0.05). A similar phenotype was observed in the offspring of mothers with pre-pregnancy weight loss via liraglutide despite ongoing consumption of the HFD during pregnancy. All methods and timing of maternal weight intervention were effective at ameliorating adverse liver effects in the offspring.
生命早期暴露于母体肥胖会使后代易患代谢相关脂肪性肝病（MAFLD）。本研究旨在确定围产期体重减轻（无论是通过饮食干预还是药物干预）是否能改善肥胖母亲的后代的不良肝脏健康结果。C57Bl/6 孕鼠喂食标准饮食或高脂肪饮食（HFD）8 周。继续喂食 HFD、转换为标准饮食或给予利拉鲁肽 4 周的 HFD 喂养的小鼠。在停止使用利拉鲁肽一周的洗脱期后诱导怀孕，在此期间所有动物仍保留在各自的饮食中。一部分 HFD 喂养的小鼠在怀孕期间转换为标准饮食。所有后代均断奶至 HFD。在产后第 12 周评估后代的人体测量、代谢和肝脏结果。肥胖母亲的后代表现出与 MAFLD 一致的表型变化。通过围产期饮食干预实现体重减轻的母亲的后代胰岛素抵抗降低（<0.001），炎症标志物（<0.001）、氧化应激（<0.05）和纤维化（<0.05）的肝表达减少。尽管在怀孕期间继续摄入 HFD，但通过利拉鲁肽进行妊娠前体重减轻的母亲的后代也观察到类似的表型。所有的母亲体重干预方法和时间都能有效改善后代的肝脏不良影响。
