Nutritional stress suppresses hepatic antioxidant defenses without affecting inflammatory signaling in periparturient fat-tailed ewes

Abstract

Ruminants experience major metabolic stress during the periparturient period, leading to negative energy balance (NEB), oxidative stress, and inflammation. While NEB is well studied in dairy cows, molecular responses to feed restriction in locally adapted fat-tailed sheep breeds remain unclear. This study aimed to study the effect of phased feed restriction and parturition on hepatic genes related to antioxidant defense, NADPH regeneration, and inflammation in Lori Bakhtiari and Turki Qashqai ewes. Twenty ewes were used in this study. The control group (Ctrl; n=10) received pre- and postpartum diets to meet 100% of the energy requirements. The Feed Restricted group (FR; n=10) received a diet to simulate a sudden energy deficit prepartum and postpartum. Liver biopsies were collected on week -3 and 3 relative to parturition. Pro-inflammatory cytokines (IL-6, IL-8, TNFα) were unaffected by FR or parturition. The hepatic mRNA expression of GCLM remained constant in the FR group but decreased in the Ctrl group postpartum. In addition, GCLM mRNA abundance was lower in the FR group compared to the Ctrl group prepartum, but higher postpartum. The hepatic mRNA expression of SRXN1 increased postpartum in the FR group but remained constant in Ctrl. In addition, SRXN1 showed higher abundance in the FR group than in the Ctrl group both prepartum and postpartum. Both hepatic mRNA expression of GPX3 and GPX4 were constant in the FR group but increased in the Ctrl group postpartum. Thus, no differences in GPX3 and GPX4 were detected between groups prepartum but were lower in the FR group compared to the Ctrl group postpartum. In addition, FR downregulated the hepatic mRNA expression of GCLC, G6PD, 6PGD, CAT, SOD1, and SOD3, while increasing GR1. Parturition decreased the hepatic mRNA expression GCLC, G6PD, 6PGD, and TXNRD1, and increased Hb, SOD1, and SOD3 mRNA abundance. Feed restriction reduced key hepatic antioxidant and NADPH-regenerating genes, while parturition further intensified oxidative processes. Despite these sudden changes in dietary energy prepartum and postpartum, inflammatory cytokines remained constant, indicating that fat-tailed ewes prioritize redox adaptation over inflammation under nutritional stress and parturition-related metabolic demands.