Dataset Information

Transcriptomic and metabolomic characterization of post-hatch metabolic reprogramming during hepatic development in the chicken.

ABSTRACT:

Background

Artificial selection of modern meat-producing chickens (broilers) for production characteristics has led to dramatic changes in phenotype, yet the impact of this selection on metabolic and molecular mechanisms is poorly understood. The first 3 weeks post-hatch represent a critical period of adjustment, during which the yolk lipid is depleted and the bird transitions to reliance on a carbohydrate-rich diet. As the liver is the major organ involved in macronutrient metabolism and nutrient allocatytion, a combined transcriptomics and metabolomics approach has been used to evaluate hepatic metabolic reprogramming between Day 4 (D4) and Day 20 (D20) post-hatch.

Results

Many transcripts and metabolites involved in metabolic pathways differed in their abundance between D4 and D20, representing different stages of metabolism that are enhanced or diminished. For example, at D20 the first stage of glycolysis that utilizes ATP to store or release glucose is enhanced, while at D4, the ATP-generating phase is enhanced to provide energy for rapid cellular proliferation at this time point. This work has also identified several metabolites, including citrate, phosphoenolpyruvate, and glycerol, that appear to play pivotal roles in this reprogramming.

Conclusions

At Day 4, metabolic flexibility allows for efficiency to meet the demands of rapid liver growth under oxygen-limiting conditions. At Day 20, the liver's metabolism has shifted to process a carbohydrate-rich diet that supports the rapid overall growth of the modern broiler. Characterizing these metabolic changes associated with normal post-hatch hepatic development has generated testable hypotheses about the involvement of specific genes and metabolites, clarified the importance of hypoxia to rapid organ growth, and contributed to our understanding of the molecular changes affected by decades of artificial selection.

SUBMITTER: Van Every HA

PROVIDER: S-EPMC8147372 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Hepatic fatty acid oxidation of yolk lipoproteins provides the main energy source for chick embryos. Post-hatching these yolk lipids are rapidly exhausted and metabolism switches to a carbohydrate-based energy source. We recently demonstrated that many microRNAs (miRNAs) are key regulators of hepatic metabolic pathways during this metabolic switching. MiRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression in most eukaryotes. To further elucidate the roles of miRNAs in the metabolic switch, we used delayed feeding for 48 h to impede the hepatic metabolic switch. We found that hepatic expression of several miRNAs including miR-33, miR-20b, miR-34a, and miR-454 was affected by delaying feed consumption for 48 h. For example, we found that delayed feeding resulted in increased miR-20b expression and conversely reduced expression of its target FADS1, an enzyme involved in fatty acid synthesis. Interestingly, the expression of a previously identified miR-20b regulator FOXO3 was also higher in delayed fed chicks. FOXO3 also functions in protection of cells from oxidative stress. Delayed fed chicks also had much higher levels of plasma ketone bodies than their normal fed counterparts. This suggests that delayed fed chicks rely almost exclusively on lipid oxidation for energy production and are likely under higher oxidative stress. Thus, it is possible that FOXO3 may function to both limit lipogenesis as well as to help protect against oxidative stress in peri-hatch chicks until the initiation of feed consumption. This is further supported by evidence that the FOXO3-regulated histone deacetylase (HDAC2) was found to recognize the FASN (involved in fatty acid synthesis) chicken promoter in a yeast one-hybrid assay. Expression of FASN mRNA was lower in delayed fed chicks until feed consumption. The present study demonstrated that many transcriptional and post-transcriptional mechanisms, including miRNA, form a complex interconnected regulatory network that is involved in controlling lipid and glucose molecular pathways during the metabolic transition in peri-hatch chicks.

Project description:Matrix metalloproteinases (MMPs) are a family of proteases, that can process extracellular matrix (ECM) components and non-ECM molecules. MMPs can also function intracellularly in proteolytic and nonproteolytic functions. The participation of MMPs in the remodeling of the chicken gastrointestinal tract is largely unknown. The aim of the present study was to examine 1) the early neonatal developmental changes and effect of delayed access to feed immediately post-hatch (PH) and 2) the effect of Eimeria infection on mRNA expression of selected MMPs, their tissue inhibitors (TIMPs), and a disintegrin and metalloproteinase (ADAM) metallopeptidase with thrombospondin type 1 motif 8 (ADAMTS8) in the gastrointestinal tract of chicken. Protein localization of MMPs and TIMPs was also carried out in the normal ileal wall at -48, 24, and 336 h relative to hatch using immunofluorescence. In experiment 1, newly hatched Ross 708 chicks received feed and water immediately PH or were subjected to 48 h delayed access to feed. Chickens were sampled at -48, 0, 4, 24, 48, 72, 96, 144, 192, 240, 288, and 336 h PH. Ileum was collected for investigation of gene expression or fixed in paraformaldehyde for immunofluorescence. In experiments 2 and 3, Ross 708 male broilers were infected, at 21 d of age with Eimeria maxima or E. acervulina or sham-infected with water. Intestinal tissues were collected at 7 and 10 d postinfection for gene expression analysis. In general, mRNA expression patterns of all examined genes showed downregulation during the first 2 wk PH and were not affected by delay in feed access. These development-dependent changes in expression and tissue-dependent localization in the ileum of selected MMPs and TIMPs indicate that these molecules participate in the remodeling of chicken intestinal tissues during PH development. Increased expression of MMP-7 and MMP-9 transcripts in the intestine of Eimeria infected birds suggests an important role for these enzymes in the process of tissue remodeling and destruction in pathological conditions. The findings of this study are important for understanding the relationship between the expression of the MMP system and intestinal development, as well its role in gastrointestinal infection and subsequent recovery.