Activation of glucocorticoid receptors is associated with the suppression of antioxidant responses in the liver of goats fed a high-concentrate diet

Abstract

This study investigated changes in oxidative stress and the relevant mechanisms in the liver of goats fed a high-concentrate (HC) diet for 5 weeks. Twelve goats were randomly assigned to a low-concentrate (concentrate-to-forage = 55:45, LC, n = 6) or HC diet (concentrate-to-forage = 90:10, n = 6), with dry matter as the base. Enzyme activity assays, real-time polymerase chain reaction and western blotting were used to evaluate antioxidant parameters and gene expression in the liver. Superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), total nitric oxide synthase activity and total antioxidant capacity (T-AOC) in the liver declined (p < .01) in HC-fed goats compared to those in LC-fed goats. The mRNA levels of GPX1, CAT and SOD1 were down-regulated (3.69, 47.37 and 27.61%, respectively) in HC-fed goats compared to those in LC-fed goats. Furthermore, glutathione S-transferase M1 (GSTM1) was upregulated (466.35%, p < .01) in the liver of HC-fed goats. The mRNA and protein levels of the nuclear factor E2-related factor 2 (NRF2) and total glucocorticoid receptor (GR) declined (p < .05) in HC-fed goats (by 28.57, 33.1, 30.85 and 34%, respectively). However, the nuclear translocation of GR increased (p < .05; by 44.75%) in HC-fed goats. Negative correlations were detected for hepatic nuclear GR protein expression with hepatic CAT activity and GPx activity. In conclusion, feeding an HC diet to goats for 5 weeks suppressed NRF2-dependent antioxidant responses and enhanced GR nuclear translocation in the liver.Highlights Feeding goats high-concentrate diets suppresses NRF2-dependent antioxidant responses in liver, downregulating NRF2 and altering SOD1, GPx and CAT activity. This suppression of NRF2-dependent antioxidant responses is associated with GR activation in the liver of goats.

Keywords

• antioxidant response
• high-concentrate diet
• nuclear factor e2-related factor 2
• glucocorticoid receptor