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Maternal and post-weaning high-fat, high-sucrose diet modulates glucose homeostasis and hypothalamic POMC promoter methylation in mouse offspring

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Abstract

Substantial evidence demonstrated that maternal dietary nutrients can significantly determine the susceptibility to developing metabolic disorders in the offspring. Therefore, we aimed to investigate the later-life effects of maternal and postweaning diets interaction on epigenetic modification of the central nervous system in the offspring. We examined the effects of dams fed a high-fat, high-sucrose (FS) diet during pregnancy and lactation and weaned to FS diet continuously until 32 weeks of age. Then, DNA methylation and gene expressions of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in the offspring. Offspring of FS diet had heavier body weight, impaired glucose tolerance, decreased insulin sensitivity and higher serum leptin level at 32-week age (p < 0.05). The expression of POMC and MC4R genes were significantly increased in offspring exposed to FS diet during gestation, lactation and into 32-week age (p < 0.05). Consistently, hypomethylation of POMC promoter in the hypothalamus occurred in the FS diet offspring (p < 0.05), compared with the C group. However, no methylation was detected of MC4R promoter in both the two groups. Furthermore, POMC-specific methylation (%) was negatively associated with glucose response to a glucose load (r = −0.273, p = 0.039). Maternal and post-weaning high-fat diet predisposes the offspring for obesity, glucose intolerance and insulin resistance in later life. Our findings can advance our thinking around the DNA methylation status of the promoter of the POMC and MC4R genes between long-term high-fat, high-sucrose diet and glucose homeostasis in mouse.

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Acknowledgments

This project was supported by National Natural Science Foundation of China (No. 81170736), National Natural Science Foundation for Young Scholars of China (No. 81300649), National Key Program of Clinical Science, and Peking Union Medical College Hospital and Postgraduate Student Innovation Fund in Peking Union Medical College (No. 2013-1002-33).

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The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Diabetes Research Center of Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, People’s Republic of China

    Jia Zheng, Xinhua Xiao, Qian Zhang, Miao Yu, Jianping Xu, Zhixin Wang, Cuijuan Qi & Tong Wang

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  1. Jia Zheng
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  2. Xinhua Xiao
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  3. Qian Zhang
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  4. Miao Yu
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  5. Jianping Xu
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  6. Zhixin Wang
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  7. Cuijuan Qi
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  8. Tong Wang
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Correspondence to Xinhua Xiao.

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Zheng, J., Xiao, X., Zhang, Q. et al. Maternal and post-weaning high-fat, high-sucrose diet modulates glucose homeostasis and hypothalamic POMC promoter methylation in mouse offspring. Metab Brain Dis 30, 1129–1137 (2015). https://doi.org/10.1007/s11011-015-9678-9

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  • DOI: https://doi.org/10.1007/s11011-015-9678-9

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