Variation in rumen epithelial fatty acid metabolism and cholesterol homeostasis contributes to different responses to the high grain diet adaptation in beef cattle

Abstract Text: Ruminal digestive disorders are common during high grain diet transition. However, little is known about the mechanism regulating this process, especially at the transcriptional level. In this study, we conducted a genome wide transcriptome comparison of ruminal epithelia when cattle were exposed to a rapid high grain transition. Transcriptome analysis of ruminal papillae, collected from 15 beef heifers when fed 3 different dietary steps during the transition (3%, 75% and 92% grain), were performed using RNA-seq. Expression of 11,044, 11,322 and 11,282 genes were detected (with reads per million (RPM) > 1 in 15 heifers of each diet) under 3%, 75% and 92% grain diet, respectively. Principle component analysis showed that the transcriptome profile of rumen epithelia between the low grain diet (LGD; 3%) and high grain diets (HGD; 75% and 92%) were different. The transition from 75% to 92% grain, the ruminal pH showed varied change patterns: decreased (DG, n = 5) or increased (UG, n = 5). When the ruminal tissue transcriptomes were compared between 75% and 92% grain diet (92% vs. 75%) in each group, the expression of some ketone body and cholesterol synthesis related genes tended to be decreased in UG (acetyl-CoA acetyl transferase 2 (ACAT2), 3-hydroxy, 3-methylglutaryl CoA synthase 1 (HMGCS1), HMG-CoA reductase (HMGCR), and farnesyl diphosphate synthase (FDPs)) (P < 0.1), while some other cholesterol biosynthesis and ketogenesis related gene tended to be increased in DG (sterol regulatory element binding transcription factor 2 (SREBF2) and HMG-CoA lyase (HMGCL)) (P < 0.1). Furthermore, the proton and cholesterol efflux related genes were increased (Na⁺/H⁺ exchanger 3 (NHE3) and ATP-binding cassette 1 (ABCA1)) in UG (P < 0.05), while the monocarboxylate transporter 4 (MCT4) showed a tendency to be decreased in DG (P< 0.1). These results suggest DG heifers may have greater intracellular cholesterol and a reduction in intracellular pH, which might imbalance the epithelial homeostatic status. Pathway analysis showed that the differentially expressed genes in DG were involved in the “T cell receptor signaling” and “complement and coagulation cascades” pathway, while UG might activate cell repair function through “p53 signaling pathway” and cell cycle arrest. Overall, the different gene networks controlling fatty acid metabolism and cholesterol homeostasis among individuals might account for the animal variation in ruminal responses during high grain diet adaptation in beef cattle.

Keywords: beef cattle, high grain diet, rumen transcriptome