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

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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 (80 μg/kg BW), whereas piglets in the control group received the same volume of saline. On day 16 of the trial, blood samples were collected 3 h 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.

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Abbreviations

AEC:

Adenylate energy charge

AKG:

α-Ketoglutarate

ADA:

Adenosine deaminase

ADP:

Adenosine diphosphate

ALT:

Alanine aminotransferase

AMP:

Adenosine monophosphate

AST:

Aspartate aminotransferase

ATP:

Adenosine triphosphate

BW:

Body weight

CAT:

Catalase

CHE:

Cholinesterase

GSH-Px:

Glutathione peroxidase

LPS:

Lipopolysaccharide

MDA:

Malondialdehyde

PBS:

Phosphate-buffered saline

SD:

Standard deviation

SOD:

Superoxide dismutase

TAN:

Total adenine nucleotide

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Acknowledgments

This research was jointly supported by National Basic Research Program of China (No. 2012CB126305), National Natural Science Foundation of China (No. 31372319, 31402084), the Hubei Provincial Key Project for Scientific and Technical Innovation (2014ABA022), Hubei Provincial Research and Development Program (No. 2010BB023), Natural Science Foundation of Hubei Province (No. 2013CFA097, 2013CFB325, 2012FFB04805, 2011CDA131), Scientific Research Program of Hubei Provincial Department of Education (D20141701), the Hubei Hundred Talent Program, Agriculture and Food Research Initiative Competitive Grants of (2014-67015-21770) of the USDA National Institute of Food and Agriculture, and Texas AgriLife Research (H-82000). All these funding agencies had no role in the design, analysis or writing of our published studies.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The use of animals for this research was approved by the Animal Care and Use Committee of Hubei Province.

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Authors and Affiliations

  1. Hubei Key Laboratory of Animal Nutrition and Feed Science, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University, Wuhan, 430023, China

    Lei Wang, Yongqing Hou, Dan Yi, Yongtang Li, Binying Ding, Huiling Zhu, Jian Liu, Hang Xiao & Guoyao Wu

  2. Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA

    Guoyao Wu

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  1. Lei Wang
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  2. Yongqing Hou
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  3. Dan Yi
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Correspondence to Yongqing Hou.

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Wang, L., Hou, Y., Yi, D. et al. Dietary supplementation with glutamate precursor α-ketoglutarate attenuates lipopolysaccharide-induced liver injury in young pigs. Amino Acids 47, 1309–1318 (2015). https://doi.org/10.1007/s00726-015-1966-5

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