Dataset Information

Multi-omics Analysis of Metabolic Characteristics and Validation of HBEGF-Mediated Regulatory Mechanisms of Metabolism during Catch-Up Growth in Small-for-Gestational-Age Infants

ABSTRACT:

Small-for-gestational-age (SGA) is a globally recognized public health concern. Infants born SGA may experience metabolic disturbances. This study elucidated the key regulatory factors and mechanisms underlying catch-up growth (CUG) and metabolic homeostasis in SGA infants. High-throughput targeted metabolomics were employed to compare the serum profiles of SGA and appropriate-for-gestational-age (AGA) neonates, identifying key metabolic pathways and associated regulatory signaling pathways enriched with differentially expressed metabolites. Liver tissue samples were collected from neonatal SGA and AGA rats. Subsequently, mRNA sequencing to identify and analyze differentially expressed genes. Heparin-binding epidermal growth factor-like growth factor (HBEGF)— a gene critically involved in metabolic processes—was significantly upregulated in SGA rat liver tissues. HBEGF silencing can suppress CUG in SGA rats and influence carbohydrate and lipid metabolism. Furthermore, metabolomic profiling was performed to investigate the role of HBEGF in metabolic regulation during CUG in individuals with SGA. Finally, the impact of HBEGF on the AKT/GSK-3β (protein kinase B/glycogen synthase kinase 3 beta) signaling pathway was explored in both in vivo and in vitro settings. This study confirms metabolic differences between SGA and AGA individuals are evident at early-life. HBEGF may be crucial in CUG progression in SGA by modulating metabolic processes via AKT/GSK-3β signaling pathway.

INSTRUMENT(S): Gas Chromatography MS - positive

PROVIDER: MTBLS13163 | MetaboLights | 2025-10-23

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13163_GC-MS_positive__metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13163_GC-MS_positive__metabolite_profiling_v2_maf.tsv	Tabular
	s_MTBLS13163.txt	Txt

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Project description:INTRODUCTION: Restricted or enhanced intrauterine growth is associated with elevated risks of early and late metabolic problems in humans. Metabolomics based on amino acid and carnitine/acylcarnitine profile may have a role in fetal and early postnatal energy metabolism. In this study, the relationship between intrauterine growth status and early metabolomics profile was evaluated.MATERIALS AND METHODS: A single center retrospective cohort study was conducted. Newborn infants were enrolled into the study and they were grouped according to their birth weight percentile as small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) infants. In all infants amino acid and carnitine/acylcarnitine profile with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were recorded and compared between groups.RESULTS: LGA infants had higher levels of glutamic acid and lower levels of ornithine, alanine and glycine (p<0.05) when compared to AGA infants. SGA infants had higher levels of alanine and glycine levels when compared with AGA and LGA infants. Total carnitine, C0, C2, C4, C5, C10:1, C18:1, C18:2, C14-OH and C18:2-OH levels were significantly higher and C3 and C6-DC levels were lower in SGA infants (p<0.05). LGA infants had higher C3 and C5:1 level; and lower C18:2 and C16:1-OH levels (p<0.05). There were positive correlations between free carnitine and phenylalanine, arginine, methionine, alanine and glycine levels (p<0.05). Also a positive correlation between ponderal index and C3, C5-DC, C14, C14:1; and a negative correlation between ponderal index and ornithine, alanine, glycine, C16:1-OH, C18:2 were shown.CONCLUSION: We demonstrated differences in metabolomics possibly reflecting the energy metabolism in newborn infants with intrauterine growth problems in the early postnatal period. These differences might be the footprints of metabolic disturbances in future adulthood.

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Multi-omics Analysis of Metabolic Characteristics and Validation of HBEGF-Mediated Regulatory Mechanisms of Metabolism during Catch-Up Growth in Small-for-Gestational-Age Infants

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