Nuclear related factor-E2 is down-regulated by hyperinsulinemic euglycemia in dairy cows

Wednesday, July 23, 2014
Exhibit Hall AB (Kansas City Convention Center)
Mousa Zarrin , Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
Olga Wellnitz , Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
Rupert M Bruckmaier , Veterinary Physiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
Abstract Text:

At the onset of lactation the liver undergoes a high load to provide metabolites for milk synthesis in dairy cows. The endocrine and metabolic changes induce inflammation that impairs liver function. The liver is protected by nuclear factor E2-related factor 2 (Nrf2), which is activated by inflammatory signals such as reactive oxygen species (ROS), and has anti-oxidative effects, diminishes inflammatory damage, neutralizes ROS, and suppresses pro-inflammatory signaling. We have studied hepatic mRNA abundance of Nrf2 as a response to long term (48 h) insulin and beta-hydroxybutyrate (BHBA) infusion in mid-lactation dairy cows. Twenty four Holstein dairy cows were randomly assigned to four intravenous treatment groups including an hyperinsulinemic clamp infusion to decrease plasma glucose concentration to 2.5 ± 0.1 mmol/L (HypoG, n=5), a hyperinsulinemic euglycemic clamp to maintain plasma glucose concentration at pre-infusion level (EUG, n=6), a BHBA infusion (HyperB, n= 5), and a 0.9 % NaCl infusion (Control, n=8). Liver tissue samples were taken one week before and 48 h after the start of infusion. Changes of hepatic mRNA abundance (RT-qPCR) of several acute-phase proteins and of Nrf2 between before and after 48 h infusions were evaluated by analysis of variance with treatment as fixed effect. SAA and Hp mRNA was up-regulated in all treatment groups (P<0.05) during 48 h infusions. The mRNA of glutathione peroxidase 3 (GPX3), metallothionein (MT) 1A, MT1E, and MT2A was up-regulated after 48 h of infusions in Control (P<0.05). Insulin infusion down-regulated mRNA abundance of microsomal glutathione S-transferase 3 (MGST3), MT1E, MT2A, NAD (P) H dehydrogenase, quinone 1 (NQO1), and superoxide dismutase 1 (SOD1) (P<0.05). Changes of GPX3, MGST3, MT1A, MT1E, MT2A, and SOD1 mRNA abundance during 48 h of infusion differed significantly between EUG and Control (P<0.05). Change of mRNA abundance of NQO1 after 48 h of infusions differed significantly between EUG and HyperB (P<0.05). Results show that infusions and experimental condition up-regulated mRNA abundance of APP in all treatments, and up-regulated some of Nrf2 in control, whereas induced hyperinsulinemic euglycemic clamp down-regulated most of Nrf2 factors in EUG. It seems that the up-regulation of these factors in Control occurs despite unchanged metabolites during the infusion. Although insulin has an anti-inflammatory role different results observed in both HypoG and EUG. It can be assumed that down-regulation of Nrf2 mRNA factors in EUG is related to a decrease of hepatic gluconeogenesis through the decline in glucagon secretion.

Keywords: liver, immune response, cow