Dietary supplementation with glutamate precursor α-ketoglutarate attenuates lipopolysaccharide-induced liver injury in young pigs.

Abstract

There is growing interest in glutamate as a functional amino acid in nutrition and health. This study was conducted to determine whether glutamate precursor α-ketoglutarate (AKG) could alleviate lipopolysaccharide (LPS)-induced liver injury in young pigs. Twenty-four piglets were randomly assigned to the control, LPS, or LPS+AKG group. Piglets in the control and LPS groups were fed a basal diet, whereas piglets in the NAC group were fed the basal diet supplemented with 1% AKG. On days 10, 12, 14, and 16 of the trial, piglets in the LPS and LPS+AKG groups received intraperitoneal administration of LPS (80μg/kg BW), whereas piglets in the control group received the same volume of saline. On day 16 of the trial, blood samples were collected 3h after LPS or saline injection. Twenty-four hours post-administration of LPS or saline (on day 17 of the trial), piglets were killed to obtain liver for analysis. Dietary AKG supplementation alleviated LPS-induced histomorphological abnormalities and mitigated LPS-induced increases in aspartate aminotransferase (AST) activity and AST/ALT ratio (P<0.05). Compared with the LPS group, dietary supplementation with AKG decreased plasma glutamate concentration, while increasing hepatic concentrations of glutamate, glutamine, leucine, asparagine, lysine, alanine, serine, threonine, valine, and phenylalanine (P<0.05). LPS challenge dramatically increased concentrations of malondialdehyde and decreased glutathione peroxidase activity in the liver. Additionally, LPS challenge enhanced concentrations of AMP and total protein, as well as RNA/DNA and total protein/DNA ratios, while decreasing hepatic ADP concentrations. These adverse effects of LPS challenge were ameliorated by AKG supplementation. Collectively, dietary AKG supplementation provides a new means to ameliorate LPS-induced liver injury by increasing anti-oxidative capacity and improving energy metabolism in young pigs.