Small-for-gestational-age (SGA) or large-for-gestational-age (LGA) infants have increased risk of type 2 diabetes mellitus in later life. The intrauterine environment provides a foundation on which chronic disease develop in adulthood, however, the molecular mechanisms still remained unsolved. We recruited 135 pregnant and their infants, and then selected 67 pairs for plasma metabolomics analysis according to the birthweight of newborns, SGA (<10th percentile, n=16), AGA (∼50th percentile, n=28) and LGA (>90th percentile, n=23). Non-targeted metabolomics were performed by UPLC-Q-TOF-MS, and the metabolites were screened by P value, fold change and VIP value in OPLS-DA model. We found a group of metabolites over-/low-expressed in both SGA and LGA groups when compared to AGA group. Cholesteryl acetate (CE) was negatively related to SGA and LGA (logistic regression, AGA=0, SGA and LGA=1) in both mothers (adj. r=-1.50, adj. p=0.03) and infants (adj. r=-1.22, adj. p=0.03). Citicoline was positively related to SGA and LGA (maternal adj. r=4.71, adj. p=0.18; fetal adj. r=0.97, adj. p=0.06). CE and citicoline were involved in glycerophospholipid metabolism (EHMN database). Dihydroxyfumaric acid (DA) reported as insulin inhibitor was over-expressed in SGA and LGA (maternal adj. r=0.72, adj. p=0.09; fetal adj. r=0.91, adj. p=0.09). Moreover, the fetal citicoline (r=-0.294, p=0.082) and CE (r=0.369, p=0.027) was associated with cord blood glucose. Fetal DA was negatively associated with HDL (r=-0.416, p=0.012) and total cholesterol (r=-0.345, p=0.039).
In conclusion, the abnormal expression of CE, citicoline and DA in SGA and LGA mothers might cause the same abnormality in fetus, and were involved in glycerophospholipid metabolism and insulin inhibition. These new findings indicated that a group of metabolites which can be passed from mother to offspring might affect the metabolic syndrome in both SGA and LGA infants.
J. Liu: None. X. Zhai: None. X. Xiao: None. M. Yu: None. N. Zhao: None. Z. Li: None. J. Fu: None. M. Deng: None. L. Zhou: None.
National Natural Science Foundation of China (81870579); Fundamental Research Funds for the Central Universities (3332018015)