Abstract
The endocrine and metabolic changes in early lactating dairy cows can induce inflammation through reactive oxygen species (ROS) impairing liver function. Nuclear erythroid 2-related factor 2 (Nrf2) is a transcription factor which regulates the expression of genes encoding antioxidative proteins which diminish inflammatory damage, neutralize ROS and suppress pro-inflammatory signaling, thereby protecting the liver. The aim was to investigate hepatic mRNA abundance of genes regulated by Nrf2 in response to a long-term (48 h) insulin or beta-hydroxybutyrate (BHB) infusion in 24 mid-lactating dairy cows. Treatments included 1) hyperinsulinemic clamp infusion (HypoG, n = 5), 2) hyperinsulinemic euglycemic clamp (EuG, n = 6), 3) BHB infusion (HyperB, n = 5), and 4) NaCl infusion (Control, n = 6). Liver tissue was sampled one week before and 48 h after the start of the infusion. Changes of hepatic mRNA abundances of candidate genes assessed via qPCR were evaluated by analysis of variance (ANOVA). Hyperinsulinemia euglycemic clamp downregulated mRNA abundance of microsomal glutathione S-transferase 3 (MGST3), MT1E, MT2A, glutathione peroxidase 3 (GPX3), superoxide dismutase 1(SOD1), catalase (CAT), and NAD (P) H dehydrogenase quinone 1(NQO1) compared to pre-infusions. The mRNA abundance of metallothionein 1A (MT1A) showed a tendency to increase in HyperB in comparison to pre-infusion level. Lower mRNA abundances of MT1E, MGST3, and SOD1 were observed in EuG compared to Control. The mRNA abundance of NQO1 was lower in EuG in comparison to HyperB. Downregulation of candidate genes could be related to reduced hepatic gluconeogenesis, since both high plasma insulin and low glucagon secretion levels were observed in EuG. Downregulation of Nrf2’s antioxidant enzymes may result in reduced liver protection, thereby contributing to impaired hepatic metabolism.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have