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J Nutr. 2016 Aug;146(8):1514-20. doi: 10.3945/jn.116.236000. Epub 2016 Jul 6.

Dietary Supplementation with α-Ketoglutarate Activates mTOR Signaling and Enhances Energy Status in Skeletal Muscle of Lipopolysaccharide-Challenged Piglets.

Author information

1
Hubei Key Laboratory of Animal Nutrition and Feed Science, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University, Wuhan, China; and.
2
Hubei Key Laboratory of Animal Nutrition and Feed Science, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University, Wuhan, China; and houyq@aliyun.com g-wu@tamu.edu.
3
Hubei Key Laboratory of Animal Nutrition and Feed Science, Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Wuhan Polytechnic University, Wuhan, China; and Department of Animal Science, Texas A&M University, College Station, TX houyq@aliyun.com g-wu@tamu.edu.

Abstract

BACKGROUND:

Skeletal muscle undergoes rapid loss in response to inflammation. α-Ketoglutarate (AKG) has been reported to enhance muscle growth in piglets, but the underlying mechanisms are largely unknown.

OBJECTIVES:

This study tested the hypothesis that dietary AKG supplementation activates mechanistic target of rapamycin (mTOR) signaling and improves skeletal muscle energy metabolism in lipopolysaccharide (LPS)-challenged piglets.

METHODS:

Forty-eight male piglets (Duroc × Landrace × Yorkshire) were weaned at 21 d of age to a corn- and soybean meal-based diet. After a 3-d period of adaptation, piglets with a mean weight of 7.21 kg were randomly assigned to control, LPS (intraperitoneal administration of 80 μg LPS/kg body weight on days 10, 12, 14, and 16), or LPS plus 1% dietary AKG (LPS+AKG) groups. On day 16, blood samples were collected from 8 piglets/group 3 h after LPS administration. On day 17, piglets were killed to obtain gastrocnemius muscle from 8 piglets/group for biochemical analysis.

RESULTS:

Compared with the control group, LPS administration increased (P < 0.05) plasma concentrations of globulin (by 14%) and tumor necrosis factor α (by 59%) and the intramuscular ratio of AMP to ATP (by 93%) and abundance of phosphorylated acetyl-coenzyme A carboxylase (ACC) β protein (by 64%). Compared with the control group, LPS administration reduced (P < 0.05) weight gain (by 15%); plasma concentrations of glutamine (by 20%), glucose (by 23%), insulin, insulin-like growth factor I, and epidermal growth factor; intramuscular concentrations of glutamine (by 27%), ATP (by 12%), ADP (by 22%), and total adenine nucleotides; and intramuscular ratios of phosphorylated mTOR to total mTOR (by 38%) and of phosphorylated 70-kDa ribosomal protein S6 kinase (p70S6K) to total p70S6K (by 39%). These adverse effects of LPS were ameliorated (P < 0.05) by AKG supplementation.

CONCLUSIONS:

Dietary AKG supplementation activated mTOR signaling, inhibited ACC-β, and improved energy status in skeletal muscle of LPS-challenged piglets. These results provide a biochemical basis for the use of AKG to enhance piglet growth under inflammatory or practical postweaning conditions.

KEYWORDS:

cell signaling; gastrocnemius muscle; inflammation; lipopolysaccharide; α-ketoglutarate

PMID:
27385764
DOI:
10.3945/jn.116.236000
[Indexed for MEDLINE]

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