Long-Term Effects of Maternal Low-Protein Diet and Post-weaning High-Fat Feeding on Glucose Metabolism and Hypothalamic POMC Promoter Methylation in Offspring Mice.
Long-Term Effects of Maternal Low-Protein Diet and Post-weaning High-Fat Feeding on Glucose Metabolism and Hypothalamic POMC Promoter Methylation in Offspring Mice.
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母体低蛋白饮食和断奶后高脂喂养对子代小鼠葡萄糖代谢和下丘脑 POMC 启动子甲基化的长期影响
DOI：
10.3389/fnut.2021.657848
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发表时间：
2021
影响因子：
5
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Zheng J;Zhang L;Liu J;Li Y;Zhang J
大量证据表明，母亲营养不良可能会增加成年后肥胖、胰岛素抵抗和2型糖尿病的易感性。越来越明显的是，大脑，特别是下丘脑，在葡萄糖稳态中起着关键作用。然而，很少有信息是已知的机制，母亲的蛋白质限制结合断奶后高脂肪（HF）喂养与脑神经递质的表达改变，并调查后代下丘脑的表观遗传修饰尚未完全阐明。本研究旨在探讨母体蛋白质限制结合断奶后高脂喂养对雄性子代小鼠糖代谢和下丘脑POMC甲基化的影响。在整个妊娠期和哺乳期，C57/BL 6小鼠喂食低蛋白（LP）或正常食物（NC）饮食。然后，将雄性后代随机断奶至NC或高脂肪（HF）饮食，直至32周龄。测定雄性后代下丘脑前阿黑皮素（POMC）和黑素皮质素受体4（MC 4 R）的基因表达和DNA甲基化。结果表明，饲喂LP饲料的母鼠雄性后代的出生体重和断奶体重均显著降低。母体蛋白质限制结合断奶后高脂肪喂养，易导致雄性后代小鼠体重增加、持续葡萄糖耐受不良（从断奶至32周龄）、高胰岛素血症和高瘦素血症。母鼠饲喂LP和生后高脂饲料的子代小鼠POMC和MC 4 R表达显著增加（P < 0.05）。此外，母体蛋白质限制结合断奶后高脂喂养诱导下丘脑POMC启动子低甲基化（P < 0.05），POMC特异性甲基化（%）与雄性后代小鼠对葡萄糖负荷的葡萄糖反应呈负相关（r =-0.42，P = 0.039）。总之，母体LP饮食结合断奶后高脂喂养易使雄性后代糖代谢受损和下丘脑POMC低甲基化。这些发现可以促进我们对母体LP饮食结合断奶后高脂喂养与后代代谢健康之间下丘脑POMC基因甲基化的思考。
Substantial evidence indicated that maternal malnutrition could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes in adulthood. It is increasingly apparent that the brain, especially the hypothalamus, plays a critical role in glucose homeostasis. However, little information is known about the mechanisms linking maternal protein restriction combined with post-weaning high-fat (HF) feeding with altered expression of brain neurotransmitters, and investigations into the epigenetic modifications of hypothalamus in offspring have not been fully elucidated. Our objective was to explore the effects of maternal protein restriction combined with post-weaning HF feeding on glucose metabolism and hypothalamic POMC methylation in male offspring mice. C57/BL6 mice were fed on either low-protein (LP) or normal chow (NC) diet throughout gestation and lactation. Then, the male offspring were randomly weaned to either NC or high-fat (HF) diet until 32 weeks of age. Gene expressions and DNA methylation of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in male offspring. The results showed that birth weights and body weights at weaning were both significantly lower in male offspring mice of the dams fed with a LP diet. Maternal protein restriction combined with post-weaning high-fat feeding, predisposes higher body weight, persistent glucose intolerance (from weaning to 32 weeks of age), hyperinsulinemia, and hyperleptinemia in male offspring mice. POMC and MC4R expressions were significantly increased in offspring mice fed with maternal LP and postnatal high-fat diet (P < 0.05). Furthermore, maternal protein restriction combined with post-weaning high-fat feeding induced hypomethylation of POMC promoter in the hypothalamus (P < 0.05) and POMC-specific methylation (%) was negatively correlated with the glucose response to a glucose load in male offspring mice (r = −0.42, P = 0.039). In conclusion, maternal LP diet combined with post-weaning high-fat feeding predisposed the male offspring to impaired glucose metabolism and hypothalamic POMC hypomethylation. These findings can advance our thinking about hypothalamic POMC gene methylation between maternal LP diet combined with post-weaning high-fat feeding and metabolic health in offspring.
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影响因子：
9.8
作者：
Xiao, Xinhua;Zhang, Zhen-Xin;Li, Wen-Hui;Feng, Kai;Sun, Qi;Cohen, Harvey Jay;Xu, Tao;Wang, Heng;Liu, Ai-Min;Gong, Xiao-Ming;Shen, Ying;Yi, Zeng
通讯作者：
Yi, Zeng
在脂肪组织中胰岛素耐药的表型后，捕获胰岛素抗性的表型后，追赶生长。
影响因子：
4.9
作者：
Berends, L. M.;Fernandez-Twinn, D. S.;Martin-Gronert, M. S.;Cripps, R. L.;Ozanne, S. E.
通讯作者：
Ozanne, S. E.
影响因子：
4.2
作者：
Claycombe, Kate J.;Uthus, Eric O.;Johnson, W. Thomas
通讯作者：
Johnson, W. Thomas
影响因子：
4
作者：
Ikenasio-Thorpe, Bettina A.;Breier, Bernhard H.;Fraser, Mhoyra
通讯作者：
Fraser, Mhoyra
影响因子：
5
作者：
Sellayah, Dyan;Dib, Lea;Cagampang, Felino R.
通讯作者：
Cagampang, Felino R.