Effects of Alpha-Ketoglutarate on Glutamine Metabolism in Piglet Enterocytes in Vivo and in Vitro

J Agric Food Chem. 2016 Apr 6;64(13):2668-73. doi: 10.1021/acs.jafc.6b00433. Epub 2016 Mar 28.

Abstract

Alpha-ketoglutarate (AKG) plays a vital part in the tricarboxylic acid cycle and is a key intermediate in the oxidation of L-glutamine (Gln). The study was to evaluate effects of AKG on Gln metabolism in vivo and in vitro. A total of twenty-one piglets were weaned at 28 days with a mean body weight (BW) of 6.0 ± 0.2 kg, and randomly divided into 3 groups: corn soybean meal based diet (CON group); the basal diet with 1% alpha-ketoglutarate (AKG treatment group); and the basal diet with 1% L-glutamine (GLN treatment group). Intestinal porcine epithelial cells-1 (IPEC-1) were incubated to investigate effects of 0.5, 2, and 3 mM AKG addition on Gln metabolism. Our results showed that there were no differences (P > 0.05) among the 3 treatments in initial BW, final BW, and average daily feed intake. However, average daily gain (P = 0.013) and gain:feed (P = 0.041) of the AKG group were greater than those of the other two groups. In comparison with the CON group, the AKG and GLN groups exhibited an improvement in villus length, mucosal thickness, and crypt depth in the jejunum of piglets. Serum concentrations of Asp, Glu, Val, Ile, Tyr, Phe, Lys, and Arg in the piglets fed the 1% AKG or Gln diet were lower than those in the CON group. Compared with the CON group, the mRNA expression of jejunal and ileal amino acid (AA) transporters in the AKG and GLN groups were significantly increased (P < 0.05). Additionally, the in vitro study showed that the addition of 0.5, 2, and 3 mM AKG dose-dependently decreased (P < 0.05) the net utilization of Gln and formulation of ammonia, Glu, Ala, and Asp by IPEC-1. In conclusion, dietary AKG supplementation, as a replacement for Gln, could improve Gln metabolism in piglet enterocytes and enhance the utilization of AA.

Keywords: alpha-ketoglutarate; amino acids; enterocytes; glutamine; piglet.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Arginine / blood
  • Aspartic Acid / blood
  • Body Weight
  • Citric Acid Cycle / physiology
  • Diet / veterinary
  • Dietary Supplements
  • Enterocytes / metabolism*
  • Glutamine / blood
  • Glutamine / metabolism*
  • Ileum / metabolism
  • Intestinal Mucosa / metabolism
  • Intestine, Small / metabolism
  • Isoleucine / blood
  • Jejunum / metabolism
  • Ketoglutaric Acids / metabolism*
  • Lysine / blood
  • Phenylalanine / blood
  • RNA, Messenger / metabolism
  • Swine
  • Tyrosine / blood
  • Valine / blood
  • Weaning

Substances

  • Amino Acids
  • Ketoglutaric Acids
  • RNA, Messenger
  • Isoleucine
  • Glutamine
  • Aspartic Acid
  • Tyrosine
  • Phenylalanine
  • Arginine
  • Valine
  • Lysine