Early high nutrition enhances grass-fed beef productivity through epigenetically regulated muscle metabolism, altered early adipogenesis, and rumen fermentation dynamics

We previously reported that high nutrition early in life enhances the growth and intramuscular fat (IMF; i.e., marbling) content of grass-fattened beef cattle. The objectives of this study were to elucidate the mechanisms determining meat traits through comprehensive investigations from multiple perspectives. Specifically, we evaluated the long-term effects of early high nutrition on IMF adipogenesis, lipid metabolism, myofibre characteristics, rumen fermentation, and epigenetic regulation. Epigenetically mediated metabolism was investigated using integrated multiomics approaches including metabolites, gene expression, and DNA methylation. Wagyu (Japanese Black) steers were allocated to two groups: early roughage (ER, n = 11) steers fed a standard amount of milk replacer until 3 months of age (mo) and only roughage from 4 to 10 mo; and early high overall nutrition (EHN, n = 12) steers provided three times the standard amount of milk replacer until 3 mo and a high-concentrate diet from 4 to 10 mo. From 11 to 31 mo, all of the steers were fed only roughage (final BW, ER: 521.9 kg, EHN: 571.3 kg, P = 0.005; IMF in longissimus thoracis muscle (LM), ER: 9.4%, EHN: 13.2%, P = 0.039). The EHN LM contained larger adipocytes from the early to the finishing period (P < 0.055), with higher expression of adipogenesis-related genes (P < 0.032), including CCAAT/enhancer binding protein alpha (C/EBPα) and peroxisome proliferator-activated receptor gamma (PPARγ). During the finishing period, EHN adipose tissues contained more monounsaturated fatty acid (P < 0.018) and EHN LM contained fewer oxidative and more glycolytic myofibres (P < 0.054). The EHN steers had a higher proportion of rumen propionate and a lower acetate/propionate ratio during the high-nutrition and late fattening periods (P < 0.046). Multiomics analysis of metabolites, mRNA transcripts, and DNA methylation identified mitochondrial β-oxidation and biogenesis declines in EHN LM as candidate epigenetically regulated metabolism. These were indicated by accumulated 9-acylcarnitines and low gene expression of acyl-CoA synthetase medium-chain family member 1 (ACSM1), enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH), 3-hydroxybutyrate dehydrogenase 1 (BDH1), and apelin receptor (APLNR; P < 0.059), all of which had differentially methylated DNA regions. These findings suggest that the increase in LM IMF might be the result of early adipocyte hyperplasia, greater nutrient supply through rumen programming of high propionate production, and epigenetic regulation of metabolism, involving decreased muscle mitochondrial function inducing a shift towards myofibres that consume less lipids.