High-fat feeding reprograms maternal energy metabolism and induces long-term postpartum obesity in mice.
High-fat feeding reprograms maternal energy metabolism and induces long-term postpartum obesity in mice.
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高脂肪喂养会重新编程母体能量代谢并诱导小鼠长期产后肥胖。
DOI：
10.1038/s41366-018-0304-x
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Shao,Jianhua
中科院分区：
文献类型：
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作者：
Qiao,Liping;Chu,Kayee;Wattez,Jean-Sebastien;Lee,Samuel;Gao,Hongfei;Feng,Gen-Sheng;HayJr,WilliamW;Shao,Jianhua
背景妊娠期体重增加过多（EGWG）与产后肥胖密切相关。然而，EGWG与产后肥胖的因果作用尚未得到实验证实。本研究的目的是确定EGWG是否以及如何导致长期产后肥胖。方法C57BL/6小鼠在妊娠期以高脂饮食（HFFDG）或对照饲料喂养，然后在分娩后监测其身体成分和能量代谢。结果我们发现HFFDG显着增加了妊娠期体重增加。分娩后，HFFDG 治疗小鼠 (Preg-HF) 的肥胖很快恢复到对照组的水平。然而，产后 3 个月，即使正常进食，Preg-HF 小鼠的体脂也开始显着增加。 Preg-HF 小鼠的体脂随着年龄的增长而增加，到分娩后 9 个月时，其体脂增加是对照组水平的 2 倍。 Preg-HF小鼠白色脂肪组织（WAT）的扩张表现为内脏脂肪增生和皮下脂肪肥大。 Preg-HF 小鼠在以后的生活中出现了低能量消耗和肩胛间棕色脂肪组织 (iBAT) 中的 UCP1 表达。尽管 Preg-HF 和对照小鼠的血液雌激素浓度相似，但在分娩 9 个月后，在 Preg-HF 小鼠的脂肪中检测到雌激素受体 α (ERα) 表达显着下降，并且 ERα 启动子过度甲基化。有趣的是，仅在妊娠末期 Preg-HF 小鼠 iBAT 和 WAT 的脂肪祖细胞中检测到 ERα 启动子高甲基化和 ERα 低表达。结论这些结果表明，HFFDG 导致长期产后肥胖，与产后早期脂肪滞留无关。这项研究还表明，HFFDG 通过表观遗传减少 BAT 和 WAT 中的雌激素信号，对长期产后能量代谢产生不利影响。
BackgroundExcessive gestational weight gain (EGWG) closely associates with postpartum obesity. However, the causal role of EGWG in postpartum obesity has not been experimentally verified. The objective of this study was to determine whether and how EGWG causes long-term postpartum obesity.MethodsC57BL/6 mice were fed with high-fat diet during gestation (HFFDG) or control chow, then their body composition and energy metabolism were monitored after delivery.ResultsWe found that HFFDG significantly increased gestational weight gain. After delivery, adiposity of HFFDG-treated mice (Preg-HF) quickly recovered to the levels of controls. However, 3 months after parturition, Preg-HF mice started to gain significantly more body fat even with regular chow. The increase of body fat of Preg-HF mice was progressive with aging and by 9 months after delivery had increased 2-fold above the levels of controls. The expansion of white adipose tissue (WAT) of Preg-HF mice was manifested by hyperplasia in visceral fat and hypertrophy in subcutaneous fat. Preg-HF mice developed low energy expenditure and UCP1 expression in interscapular brown adipose tissue (iBAT) in later life. Although blood estrogen concentrations were similar between Preg-HF and control mice, a significant decrease in estrogen receptor α (ERα) expression and hypermethylation of the ERα promoter was detected in the fat of Preg-HF mice 9 months after delivery. Interestingly, hypermethylation of ERα promoter and low ERα expression were only detected in adipocyte progenitor cells in both iBAT and WAT of Preg-HF mice at the end of gestation.ConclusionsThese results demonstrate that HFFDG causes long-term postpartum obesity independent of early postpartum fat retention. This study also suggests that HFFDG adversely programs long-term postpartum energy metabolism by epigenetically reducing estrogen signaling in both BAT and WAT.