Elevated hepatic lipid peroxidation and oxidative stress in underperforming piglets

Abstract Text:

The present study was designed to determine if normal weight pigs that grow poorly during the pre-weaning period have altered hepatic metabolism, as previously reported for intrauterine growth retarded pigs relative to littermates with normal growth rates.  Eight pairs of average birth weight pigs (1.57 ± 0.05 kg) were identified that diverged in weight by a minimum of 50 g/day until 21 days of age.  At 21 days, slow growing (SG) pigs weighed 5.47 ± 0.22 kg while control littermates weight 6.98 ± 0.28 kg (P < 0.001).  Livers were collected for analysis at day 21 for analysis of enzyme activity, glycogen content and gene expression.  Metabolomic analysis of the liver tissue was performed by Metabolon (Durham, NC).  No changes with growth rate were detected in liver enzyme activity per mg tissue protein for enzymes in glycolysis, lipogenesis or the pentose phosphate shunt (P > 0.05).  Liver glycogen content (mg/gm liver protein) was similar between SG piglets and control littermates (P = 0.908).  The mRNA abundance for the two genes regulating peroxisomal fatty acid oxidation: acyl CoA oxidase 1 (ACOX1; P < 0.001) and peroxisome proliferator-activated receptor α (PPARα; P <= 0.003), superoxide dismutase 2 (P = 0.021), lactate dehydrogenase (P = 0.016) , insulin-like growth factor 2 (IGF2; P = 0.002), IGF binding protein 2 (IGFBP2; P = 0.004) and IGFBP3 (P = 0.015) were increased in the liver of the SG piglet relative to liver of piglets experiencing normal growth, as measured by real-time quantitative PCR.  The increases in PPARα and ACOX1 mRNA abundance suggest that the liver of the SG piglet has the capacity to oxidize an increased proportion of long chain fatty acids relative to the control piglet through peroxisomal β-oxidation.  The parallel increase in SOD2 mRNA abundance suggests that SOD2 may function to reduce the oxidative stress caused by an increase in peroxisomal β-oxidation.  Metabolomic analysis of the liver from these SG piglets confirmed an increase in mono- and dihydroxy- fatty acids indicative of increased lipid peroxidation and oxidative stress relative to liver from control littermates (p < 0.05).  These data indicate that the SG piglet utilizes alternative pathways for fatty acid oxidation during the preweaning period which may be a predictor for poor postnatal growth or a target for treatment to improve growth.

Keywords: growth, liver, lipid peroxidation, oxidative stress, pig,