Role of metabolic and cellular proliferation genes in ruminal development in response to enhanced plane of nutrition in neonatal Holstein calves

A. Naeem, J. K. Drackley, J. Stamey, J. J. Loor

Research output: Contribution to journalArticlepeer-review


We evaluated expression of 50 genes encoding enzymes involved in metabolism, cellular growth, and various transporters in ruminal epithelium tissue when calves were fed conventional milk replacer (MR) and starter (control) or enhanced MR and enhanced starter. Male Holstein calves were fed reconstituted control MR [20% crude protein (CP), 20% fat; 0.57kg of solids/calf] plus conventional starter (19.6% CP, dry matter basis) or a high-protein MR (ENH; 28.5% CP, 15% fat; at ∼2% of body weight) plus high-CP starter (25.5% CP, dry matter basis). Groups of calves in control and ENH were harvested after 43 d (wk 5) and 71 d (wk 10) of feeding. Ruminal epithelium from 5 calves (3 to 42 d age) in each group was used for transcript profiling using quantitative reverse transcription PCR. No differences were observed for plasma β-hydroxybutyrate (BHBA) concentration but BHBA increased by wk 10 regardless of treatment. Reticulorumen mass postweaning was greater in calves consuming the ENH diet and corresponded with overall greater serum insulin. A marked upregulation of the ketogenic genes HMGCS2, HMGCL, and BDH1 was observed, concomitant with downregulation of expression of genes involved in fatty acid oxidation (CPT1A, ACADVL) at wk 10. Higher relative percentage mRNA abundance of HMGCS2 (∼40% of total genes assayed), the rate-controlling enzyme in hepatic ketogenesis, underscored its importance for ruminal cell energy metabolism. Higher PPARA expression and blood nonesterified fatty acids at wk 5 due to ENH were suggestive of more extensive long-chain fatty acid oxidation in ruminal epithelial cells during the milk-fed phase. In contrast, calves fed control consumed more starter during the milk-fed phase, which likely increased production of volatile fatty acids and accounted for higher expression of propionyl-CoA carboxylase (PCCA) and the Na +/H + exchanger 2 (SLC9A2) at wk 5. Expression of G-coupled protein receptors for short-chain fatty acids was undetectable. The expression of the urea transporter (SLC14A1) increased markedly with age and was correlated with the increase in blood urea N. Expression of genes involved in cell proliferation (INSR, FOXO1, AKT3) was greater for ENH primarily during the milk-fed period and corresponded with greater serum insulin. The greater reticuloruminal mass in calves fed ENH postweaning underscores the importance of feeding high-quality starter and indicates that fermentability of the diet, by providing metabolic fuel for ruminal epithelial cells, is a primary driver of ruminal development postweaning. From a mechanistic standpoint, the 7-fold increase in expression of the nuclear receptor PPARD (∼40-fold more abundant than PPARA) suggests a key role in controlling biological processes driving ruminal epithelial cell development. Elucidating ligands of PPARD may provide the means for nutritional regulation of rumen development.

Original languageEnglish (US)
Pages (from-to)1807-1820
Number of pages14
JournalJournal of Dairy Science
Issue number4
StatePublished - Apr 2012


  • Calf
  • Rumen development
  • Ruminal epithelium

ASJC Scopus subject areas

  • Food Science
  • Animal Science and Zoology
  • Genetics


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