Anti-ACAT1 monoclonal antibody, clone BU2.I22

The transition from a high forage to a high concentrate diet is an important milestone for beef cattle moving from a stocker system to the feedlot. However, little is known about how this transition affects the rumen epithelial gene expression. This study assessed the effects of the transition from a high forage to a high concentrate diet as well as the transition from a high concentrate to a high forage diet on a variety of genes as well as ruminal papillae morphology in rumen fistulated Jersey steers. Jersey steers (n = 5) were fed either a high forage diet (80% forage and 20% grain) and transitioned to a high concentrate diet (20% forage and 80% grain) or a high concentrate diet (40% forage and 60% grain) and transitioned to a high forage diet (100% forage). Papillae from the rumen were collected for histology and RT-qPCR analysis. Body weight had a tendency for significant difference (p = .08). Histological analysis did not show changes in papillae length or width in steers transitioning from a high forage to a high concentrate diet or vice versa (p > .05). Genes related to cell membrane structure (CLDN1, CLDN4, DSG1), fatty acid metabolism (CPT1A, ACADSB), glycolysis (PFKL), ketogenesis (HMGCL, HMGCS2, ACAT1), lactate/pyruvate (LDHA), oxidative stress (NQO1), tissue growth (AKT3, EGFR, EREG, IGFBP5, IRS1) and the urea cycle (SLC14A1) were considered in this study. Overall, genes related to fatty acid metabolism (ACADSB) and growth and development (AKT3 and IGFBP5) had a tendency for a treatment x day on trial interaction effect. These profiles may be indicators of rumen epithelial adaptations in response to changes in diet. In conclusion, these results indicate that changes in the composition of the diet can alter the expression of genes with specific functions in rumen epithelial metabolism.

Acetoacetyl-CoA thiolase also known as acetyl-CoA acetyltransferase (ACAT) corresponds to two enzymes, one cytosolic (ACAT2) and one mitochondrial (ACAT1), which is thought to catalyse reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA during ketogenesis and ketolysis respectively. In addition to this activity, ACAT1 is also involved in isoleucine degradation pathway. Deficiency of ACAT1 is an inherited metabolic disorder, which results from a defect in mitochondrial acetoacetyl-CoA thiolase activity and is clinically characterized with patients presenting ketoacidosis. In this review I discuss the recent findings, which unexpectedly expand the known functions of ACAT1, indicating a role for ACAT1 well beyond its classical activity. Indeed ACAT1 has recently been shown to possess an acetyltransferase activity capable of specifically acetylating Pyruvate DeHydrogenase (PDH), an enzyme involved in producing acetyl-CoA. ACAT1-dependent acetylation of PDH was shown to negatively regulate this enzyme with a consequence in Warburg effect and tumor growth. Finally, the elevated ACAT1 enzyme activity in diverse human cancer cell lines was recently reported. These important novel findings on ACAT1's function and expression in cancer cell proliferation point to ACAT1 as a potential new anti-cancer target.