Maternal exposure to high-fat diet during pregnancy and lactation predisposes normal weight offspring mice to develop hepatic inflammation and insulin resistance.
Maternal exposure to high-fat diet during pregnancy and lactation predisposes normal weight offspring mice to develop hepatic inflammation and insulin resistance.
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母鼠在妊娠期和哺乳期暴露于高脂肪饮食中，会使正常体重的后代小鼠发生肝脏炎症和胰岛素抵抗。
DOI：
10.14814/phy2.14811
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发表时间：
2021-03
影响因子：
2.5
通讯作者：
Kim JK
中科院分区：
文献类型：
--
作者：
Saengnipanthkul S;Noh HL;Friedline RH;Suk S;Choi S;Acosta NK;Tran DA;Hu X;Inashima K;Kim AM;Lee KW;Kim JK
越来越多的证据表明，围产期营养环境与后代代谢结果之间存在潜在联系。在这里，我们研究了围产期母体喂养高脂肪饮食（HFD）对断奶和成年早期雄性子代小鼠肝脏代谢和炎症的影响。雌性 C57BL/6 J 小鼠在交配前以及怀孕和哺乳期间喂食 HFD 或正常食物 (NC) 4 周。雄性后代小鼠断奶后采用NC饮食，并在成年早期进行代谢和分子实验。出生后第 21 天，与 NC 喂养的母鼠 (Off-NC) 的雄性子代小鼠相比，HFD 喂养的母鼠 (Off-HFD) 的雄性子代小鼠全身脂肪量以及空腹血糖、胰岛素和胆固醇水平显着增加。 RT-qPCR 分析显示 Off-HFD 小鼠的肝脏炎症标志物（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 表达升高了五倍。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。相比之下，Off-HFD 小鼠中 CPT1a mRNA 水平降低了 60%。在出生后第 70 天，尽管 Off-HFD 小鼠的体重与 Off-NC 小鼠相当，但与 Off-NC 小鼠相比，Off-HFD 小鼠出现了肝脏炎症，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，肝脏胰岛素作用和骨骼肌和棕色脂肪中胰岛素刺激的葡萄糖摄取存在缺陷，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，母亲在怀孕和哺乳期间接触 HFD 对正常体重子代小鼠的代谢稳态具有隐藏的持久影响。我们研究了围产期母体喂养高脂肪饮食（HFD）对断奶和成年早期雄性后代小鼠肝脏代谢和炎症的影响。 HFD 的后代在断奶时显示出肥胖、空腹血糖和胆固醇水平短暂增加。年轻的成年雄性小鼠出现了全身性胰岛素抵抗，并伴有肝脏胰岛素作用缺陷以及骨骼肌和棕色脂肪组织中胰岛素刺激的葡萄糖摄取缺陷。我们的研究结果表明，母亲接触 HFD 对正常体重子代小鼠的代谢稳态存在隐藏的持久影响。
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. 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. Offspring from HFD showed transient increase in adiposity, fasting blood glucose, and cholesterol levels at weaning. Young adult male mice developed systemic insulin resistance with defects in hepatic insulin action and insulin‐stimulated glucose uptake in skeletal muscle and brown adipose tissue. Our findings indicate hidden, lasting effects of maternal exposure to HFD on metabolic homeostasis of normal weight offspring mice.
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DOI：
10.1111/obr.12524
发表时间：
2017-06
期刊：
Obesity reviews : an official journal of the International Association for the Study of Obesity
影响因子：
--
作者：
Ribaroff GA;Wastnedge E;Drake AJ;Sharpe RM;Chambers TJG
通讯作者：
Chambers TJG
影响因子：
29
作者：
Mauvais-Jarvis F;Arnold AP;Reue K
通讯作者：
Reue K
影响因子：
3.7
作者：
Tao R;Xiong X;Harris RA;White MF;Dong XC
通讯作者：
Dong XC
影响因子：
6.1
作者：
Zou, Yuhong;Li, Jun;Wang, Yuanyuan
通讯作者：
Wang, Yuanyuan
影响因子：
4.8
作者：
Kruse, Michael;Seki, Yoshinori;Charron, Maureen J.
通讯作者：
Charron, Maureen J.