title: Maternal Low-Protein Diet Modulates Glucose Metabolism and Hepatic MicroRNAs Expression in the Early Life of Offspring †.
abstract: Emerging studies revealed that maternal protein restriction was associated with increased risk of type 2 diabetes mellitus in adulthood. However, the mechanisms of its effects on offspring, especially during early life of offspring, are poorly understood. Here, it is hypothesized that impaired metabolic health in offspring from maternal low-protein diet (LPD) is associated with perturbed miRNAs expression in offspring as early as the weaning age. We examined the metabolic effects on the C57BL/6J mice male offspring at weaning from dams fed with LPD or normal chow diet (NCD) throughout pregnancy and lactation. Maternal LPD feeding impaired metabolic health in offspring. Microarray profiling indicated that mmu-miR-615, mmu-miR-124, mmu-miR-376b, and mmu-let-7e were significantly downregulated, while, mmu-miR-708 and mmu-miR-879 were upregulated in LPD offspring. Bioinformatic analysis showed target genes were mapped to inflammatory-related pathways. Serum tumor necrosis factor-α (TNF-α) levels were higher and interleukin 6 (IL-6) had a tendency to be elevated in the LPD group. Finally, both mRNA and protein levels of IL-6 and TNF-α were significantly increased in the LPD group. Our findings provide novel evidence that maternal LPD can regulate miRNAs expression, which may be associated with chronic inflammation status and metabolic health in offspring as early as the weaning age.
authors.affiliation: 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, Beijing 100730, China. zhengjiapumc@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Zheng
authors.affiliation: 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, Beijing 100730, China. xiaoxinhua@medmail.com.cn.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xiao
authors.affiliation: 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, Beijing 100730, China. rubiacordifolia@yahoo.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: 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, Beijing 100730, China. tongtong0716@sina.com.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: 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, Beijing 100730, China. yumiao@mendmail.com.cn.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: 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, Beijing 100730, China. jpxuxh@163.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D050260:Carbohydrate Metabolism; D003924:Diabetes Mellitus, Type 2; D004032:Diet; D018753:Diet, Protein-Restricted; D005260:Female; D005786:Gene Expression Regulation; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007774:Lactation; D008099:Liver / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014886:Weaning
chemical_list: D001786:Blood Glucose; D007328:Insulin; D015850:Interleukin-6; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C583909:mirnlet7e microRNA, mouse
keywords: early life; inflammation; maternal low-protein diet; metabolic health; microRNAs; offspring