title: Dietary Supplementation with α-Ketoglutarate Activates mTOR Signaling and Enhances Energy Status in Skeletal Muscle of Lipopolysaccharide-Challenged Piglets.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Dan
authors.initials: D
authors.lastname: Yi
authors.affiliation: 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.
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Hou
authors.affiliation: 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.
authors.forename: Binying
authors.initials: B
authors.lastname: Ding
authors.affiliation: 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.
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Baocheng
authors.initials: B
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Huiling
authors.initials: H
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019587:Dietary Supplements; D004734:Energy Metabolism / Q000187:drug effects*; D005916:Globulins / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014886:Weaning
chemical_list: D005916:Globulins; D007656:Ketoglutaric Acids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D000103:Acetyl-CoA Carboxylase
keywords: cell signaling; gastrocnemius muscle; inflammation; lipopolysaccharide; α-ketoglutarate