Multi-omics profiling highlights lipid metabolism alterations in pigs fed low-dose antibiotics

Abstract

Background In order to study the relations of hepatocellular functions, weight gain and metabolic imbalance caused by low-dose antibiotics (LDA) via epigenetic regulation of gene transcription, 32 weaned piglets were employed as animal models and randomly allocated into two groups with diets supplemented with 0 or LDA (chlorotetracycline and virginiamycin). Results During the 4 weeks of the experiment, LDA showed a clear growth-promoting effect, which was exemplified by the significantly elevated body weight and average daily gain. Promoter methylome profiling using liquid hybridization capture-based bisulfite sequencing (LHC-BS) indicated that most of the 745 differential methylation regions (DMRs) were hypermethylated in the LDA group. Several DMRs were significantly enriched in genes related with fatty acids metabolic pathways, such as FABP1 and PCK1. In addition, 71 differentially expressed genes (DEGs) were obtained by strand-specific transcriptome analysis of liver tissues, including ALOX15, CXCL10 and NNMT, which are three key DEGs that function in lipid metabolism and immunity and which had highly elevated expression in the LDA group. In accordance with these molecular changes, the lipidome analyses of serum by LC-MS identified 38 significantly differential lipids, most of which were downregulated in the LDA group. Conclusions Our results indicate that LDA could induce epigenetic and transcriptional changes of key genes and lead to enhanced efficiency of lipid metabolism in the liver.

1H NMR Metabolomics on Pigs’ Liver Exposed to Antibiotics Administration: An Explorative Study

“…In addition to liver metabolome, the transcriptomic analysis provided insights for the understanding of enzyme regulation in the case of antimicrobial treatment. According to Hu et al (2020), the transcriptome and DNA methylome analysis of pigs' liver fed with low-dose of antibiotics displayed an increase in nicotinamide N-methyltransferase (NNMT) expression, a positive regulator of gluconeogenesis in primary hepatocytes, which could stabilize the Sirtuin 1 protein necessary for glucose and cholesterol metabolism to reduce the abundance of cholesterol in serum and liver [57,58]. The higher levels of glucose and the lower levels of cholesterol in the livers of pigs in the TX group could be supported by the role of NNMT, considering that liver is the organ characterized by the strongest expression of this enzyme [57,58].…”

“…According to Hu et al (2020), the transcriptome and DNA methylome analysis of pigs' liver fed with low-dose of antibiotics displayed an increase in nicotinamide N-methyltransferase (NNMT) expression, a positive regulator of gluconeogenesis in primary hepatocytes, which could stabilize the Sirtuin 1 protein necessary for glucose and cholesterol metabolism to reduce the abundance of cholesterol in serum and liver [57,58]. The higher levels of glucose and the lower levels of cholesterol in the livers of pigs in the TX group could be supported by the role of NNMT, considering that liver is the organ characterized by the strongest expression of this enzyme [57,58]. Additionally, liver boasts of an excellent production of metabolic substrates for energy metabolism (i.e., fatty acids), which are made available during stressful situations to support the organism [49].…”

Identification of critical lncRNAs for milk fat metabolism in dairy cows using WGCNA and the construction of a ceRNAs network

“…Inhibiting ALOX12 can inhibit acetyl‐CoA carboxylase 1 (ACC1) activity and lipid synthesis by activating AMP‐activated protein kinase (AMPK). Hu et al (2020) performed a transcriptomic analysis of porcine liver tissue. They identified the DEG ALOX15 as a critical gene in lipid metabolism and immunity.…”

The Metabolomics Approaches Based on LC-MS/MS for Analysis of Non-Halal Meats in Food Products: A Review

“…The lipidome analysis of serum by LC-MS was carried out separately in ESI+ and ESI− modes. OPLS-DA was executed to observe the metabolomic differentiation between the low-dose antibiotics groups and control groups, which presented clear separations in lipid profiles between the two groups [67]. The use of LC-Orbitrap MS and fourier transformation near-infrared spectroscopy (FT-NIRS) with chemometrics were also implemented to determine the geographic origin of Boston butt pork, in the study by Hye et al Korean and foreign Boston butt samples were distinguished using a biomarker analysis approach.…”