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Maternal high-calorie diet is associated with altered hepatic microRNA expression and impaired metabolic health in offspring at weaning age

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Abstract

High-calorie diet (HCD) feeding in mice predisposes offspring for impaired glucose homeostasis and obesity. However, the mechanisms underlying these detrimental effects of maternal nutrition, especially during early life of offspring, are incompletely understood. MicroRNAs (miRNAs) are small non-coding RNAs that can regulate target gene expression. Here we hypothesized that impaired metabolic health in offspring from HCD-fed dams at weaning is associated with dysregulated expression of hepatic miRNAs. Dams were fed a chow diet (CD; 11.4 % kcal fat, 62.8 % from carbohydrate, 25.8 % from protein) or HCD (58 % kcal from fat; 25.6 % from carbohydrate, 16.4 % from protein) during gestation and lactation, and metabolic health was assessed in male offspring at weaning. Hepatic levels of miRNAs and target genes were investigated in offspring from CD- or HCD-fed dams using gene and protein expression. Maternal HCD feeding impaired metabolic health in offspring compared to offspring from CD-fed dams. Microarray analysis indicated that expressions of miR-615-5p, miR-3079-5p, miR-124*, and miR-101b* were downregulated, whereas miR-143* was upregulated, in livers from offspring from HCD-fed dams. Our functional enrichment analysis indicated that the target genes of these differentially expressed miRNAs, including tumor necrosis factor-α (TNF-α) and mitogen-activated protein kinase 1 (MAPK1), were mapped to inflammatory pathways. Finally, we verified that both mRNA and protein levels of the pro-inflammatory modulators TNF-α and MAPK1 were significantly increased in livers of offspring from HCD-fed dams at weaning. Maternal HCD feeding predisposes offspring to a higher body weight and impaired glucose metabolism at weaning. To the best of knowledge, our study is the first to show that maternal HCD consumption impairs metabolic health, modulates hepatic miRNA expression, and increases markers of hepatic inflammation in offspring as early as at weaning age.

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Acknowledgments

This project was supported by the National Natural Science Foundation of China (No. 81570715 and No. 81170736) and the National Natural Science Foundation for Young Scholars of China (No. 81300649), the National Key Program of Clinical Science and Peking Union Medical College Hospital.

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  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 and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China

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

  2. Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA

    Joram D. Mul

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  1. Jia Zheng
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Zheng, J., Zhang, Q., Mul, J.D. et al. Maternal high-calorie diet is associated with altered hepatic microRNA expression and impaired metabolic health in offspring at weaning age. Endocrine 54, 70–80 (2016). https://doi.org/10.1007/s12020-016-0959-9

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