PSXII-3 - Identification of key metabolic mediators during dietary tryptophan supplementation in low birth weight pigs by RNA sequencing

Low birth weight (LBW) is associated with the development of metabolic syndrome, diabetes mellitus and insulin resistance. While tryptophan (Trp), one of essential amino acids supplied by diet, plays an essential role in fetal growth and development, the effects of Trp supplementation on metabolic processes of postnatal LBW individuals remain unclear. The objective of this study was to identify differentially expressed (DE) genes and altered biological processes in liver of LBW and normal birth weight (NBW) piglets supplemented with Trp. RNA was isolated from liver tissues of three weeks old piglets supplemented with Trp (NBW-0% and LBW-0, 0.4, and 0.8%) and was used for RNA sequencing (RNAseq). There were 100, 191 and 39 DE genes in NBW (N0) and LBW tryptophan 0.4%, 0.8% (L4 and L8) when compared to LBW without Trp supplementation (L0). To determine whether Trp supplementation can resume metabolic regulation-related gene expression to N0 level, DE genes from N0 vs. L0 were clustered into 3 groups based on co-expression trends and clusters were enriched for genes associated with lipid catabolic process, circadian regulation of gene expression and fatty acid response. Further, eight hub genes (PID1, PAFAH2, MAP3K15, ANKRD44, CYP2J34, N4BP2L1, RUSC1 and SALL1) identified in co-expression networks based on Pearson correlation coefficient had strong co-expression coefficients (|r| > 0.9) with each other. In particular, PID1 was significantly associated with many neurological, metabolic, environmental and cardiovascular traits based on phenome-wide association analysis (Phe-WAS). In summary, our study provides novel insights into the molecular mechanism underlying LBW metabolic changes with Trp supplementation in porcine liver tissue and highlights that LBW metabolism restoration may be regulated by genes participating in fatty acid response and cardiovascular diseases.