Liver transcriptomic and proteomic profiles of preweaning lambs are modified by milk replacer restriction

Prenatal and early postnatal nutrition may promote long-term effects on both feed efficiency and health of animals. Therefore, moderated milk replacer restriction during the artificial rearing period might negatively affect feed efficiency during the postweaning phases in dairy ewes. The aim of this work was to identify differentially expressed (DE) genes by RNA sequencing and differentially accumulated proteins using MALDI-TOF mass spectrometry in the liver of artificially reared Assaf lambs to identify modified metabolic pathways as a consequence of milk replacer restriction in order to find possible solutions to correct any detrimental effect caused by this factor. Forty female Assaf lambs were used in this experiment. The animals were penned individually and assigned randomly to 1 of 2 treatments groups (n = 20 per treatment). The first group of lambs was fed ad libitum (AL), whereas the second (restricted, RES) only received approximately 62.5% of the level of intake measured in the AL group. Eight 35-d-old lambs from each group (16 lambs in total) were harvested and a piece of liver of 8 lambs (4 AL and 4 RES lambs) was excised for transcriptomic and proteomic analysis. Differential gene expression analysis identified 386 DE genes [198 of them being annotated genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway], with 176 downregulated and 210 upregulated in the early feed-restricted group relative to the AL group. A total of 26 spots were also differentially accumulated proteins in the liver of the 2 groups of lambs, 10 of them being down-accumulated whereas the other 16 evolved in the opposite way in the liver of RES relative to AL lambs. Collectively, both the transcriptomic and proteomic approaches revealed an upregulation of genes participating in oxidation of fatty acids in the early feed-restricted lambs. The expression of many genes involved in the degradation of several AA (e.g. alanine, valine, isoleucine, tyrosine) was also modified in the RES lambs, probably to render substrates for gluconeogenesis. Moreover, other genes involved in apoptosis, inflammation, or hepatic oxidative pathways were upregulated in these lambs. Finally, the expression of genes implicated in oxidative phosphorylation was modified in RES animals. Altogether all these modifications suggest that the partitioning and utilization of nutrients in the early feed-restricted lambs might have been modified, being partially responsible for changes during the replacement phase later in life.