Division of Nutrition, Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Physiol Rep. 2021 Mar;9(6):e14811. doi: 10.14814/phy2.14811.
Increasing evidence shows a potential link between the perinatal nutrient environment and metabolic outcome in offspring. Here, we investigated the effects of maternal feeding of a high-fat diet (HFD) during the perinatal period on hepatic metabolism and inflammation in male offspring mice at weaning and in early adulthood. Female C57BL/6 J mice were fed HFD or normal chow (NC) for 4 weeks before mating and during pregnancy and lactation. The male offspring mice were weaned onto an NC diet, and metabolic and molecular experiments were performed in early adulthood. At postnatal day 21, male offspring mice from HFD-fed dams (Off-HFD) showed significant increases in whole body fat mass and fasting levels of glucose, insulin, and cholesterol compared to male offspring mice from NC-fed dams (Off-NC). The RT-qPCR analysis showed two- to fivefold increases in hepatic inflammatory markers (MCP-1, IL-1β, and F4/80) in Off-HFD mice. Hepatic expression of G6Pase and PEPCK was elevated by fivefold in the Off-HFD mice compared to the Off-NC mice. Hepatic expression of GLUT4, IRS-1, and PDK4, as well as lipid metabolic genes, CD36, SREBP1c, and SCD1 were increased in the Off-HFD mice compared to the Off-NC mice. In contrast, CPT1a mRNA levels were reduced by 60% in the Off-HFD mice. At postnatal day 70, despite comparable body weights to the Off-NC mice, Off-HFD mice developed hepatic inflammation with increased expression of MCP-1, CD68, F4/80, and CD36 compared to the Off-NC mice. Despite normal body weight, Off-HFD mice developed insulin resistance with defects in hepatic insulin action and insulin-stimulated glucose uptake in skeletal muscle and brown fat, and these metabolic effects were associated with hepatic inflammation in Off-HFD mice. Our findings indicate hidden, lasting effects of maternal exposure to HFD during pregnancy and lactation on metabolic homeostasis of normal weight offspring mice.
越来越多的证据表明，围产期营养环境与后代的代谢结果之间存在潜在联系。在这里，我们研究了母体在围产期喂养高脂肪饮食（HFD）对断奶后和成年早期雄性仔鼠肝脏代谢和炎症的影响。雌性 C57BL/6J 小鼠在交配前和怀孕期间以及哺乳期喂食 HFD 或正常饮食（NC）4 周。雄性仔鼠断奶后喂食 NC 饮食，成年早期进行代谢和分子实验。在产后第 21 天，来自 HFD 喂养母鼠的雄性仔鼠（Off-HFD）的全身脂肪质量和空腹血糖、胰岛素和胆固醇水平显著增加，而来自 NC 喂养母鼠的雄性仔鼠（Off-NC）则没有。RT-qPCR 分析显示，Off-HFD 小鼠肝脏中的炎症标志物（MCP-1、IL-1β 和 F4/80）增加了两到五倍。与 Off-NC 小鼠相比，Off-HFD 小鼠的肝脏 G6Pase 和 PEPCK 表达增加了五倍。与 Off-NC 小鼠相比，Off-HFD 小鼠的肝脏 GLUT4、IRS-1 和 PDK4 以及脂质代谢基因 CD36、SREBP1c 和 SCD1 的表达增加。相反，Off-HFD 小鼠的 CPT1a mRNA 水平降低了 60%。在产后第 70 天，尽管体重与 Off-NC 小鼠相当，但 Off-HFD 小鼠发生了肝炎症，与 Off-NC 小鼠相比，MCP-1、CD68、F4/80 和 CD36 的表达增加。尽管体重正常，Off-HFD 小鼠仍出现胰岛素抵抗，表现为肝脏胰岛素作用缺陷和骨骼肌及棕色脂肪中胰岛素刺激的葡萄糖摄取受损，这些代谢效应与 Off-HFD 小鼠的肝脏炎症有关。我们的研究结果表明，母体在怀孕期间和哺乳期暴露于 HFD 会对正常体重仔鼠的代谢稳态产生潜在的、持久的影响。
