title: Dietary alpha-ketoglutarate supplementation ameliorates intestinal injury in lipopolysaccharide-challenged piglets.
abstract: Neonates are at increased risk for inflammatory bowel disease, but effective prevention and treatments are currently limited. This study was conducted with the lipopolysaccharide (LPS)-challenged piglet model to determine the effects of dietary supplementation with alpha-ketoglutarate (AKG) on the intestinal morphology and function. Eighteen 24-day-old pigs (weaned at 21 days of age) were assigned randomly to control, LPS, and LPS + AKG groups. The piglets in the control and LPS groups were fed a corn- and soybean meal-based diet, whereas the LPS + AKG group was fed the basal diet supplemented with 1% AKG. On days 10, 12, 14, and 16, piglets in the LPS and LPS + AKG groups received intraperitoneal administration of LPS (80 microg/kg BW), whereas piglets in the control group received the same volume of saline. On day 16, D-xylose was orally administrated to all pigs at the dose of 0.1 g/kg BW, 2 h after LPS or saline injection, and blood samples were collected 3 h thereafter. Twenty-four hours post-administration of LPS or saline, pigs were killed to obtain intestinal mucosae for analysis. Compared with the control group, LPS challenge reduced (P < 0.05) protein levels, the ratio of villus height to crypt depth, and the ratio of phosphorylated mTOR to total mTOR in duodenal, jejunal, and ileal mucosa. These adverse effects of LPS were attenuated (P < 0.05) by AKG supplementation. Moreover, AKG prevented the LPS-induced increase in intestinal HSP70 expression. Collectively, these novel results indicate that dietary supplementation with 1% AKG activates the mTOR signaling, alleviates the mucosal damage, and improves the absorptive function of the small intestine in LPS-challenged piglets. The findings not only help understand the mode of AKGs actions in the neonatal gut but also have important implications for infant nutrition under inflammatory conditions.
authors.affiliation: Hubei key Laboratory of Animal Nutrition and Feed Science, Wuhan Polytechnic University, 430023, Wuhan, China. houyq777@yahoo.com.cn
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Hou
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Binying
authors.initials: B
authors.lastname: Ding
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
authors.forename: Huiling
authors.initials: H
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Yongtang
authors.initials: Y
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
authors.forename: Yulong
authors.initials: Y
authors.lastname: Yin
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019587:Dietary Supplements; D004386:Duodenum / Q000737:chemistry; D004435:Eating / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D007082:Ileum / Q000737:chemistry; D007410:Intestinal Diseases / Q000139:chemically induced / Q000517:prevention & control; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D007583:Jejunum / Q000737:chemistry; D007656:Ketoglutaric Acids / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000633:toxicity*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D013552:Swine; D058570:TOR Serine-Threonine Kinases; D014886:Weaning; D015430:Weight Gain / Q000187:drug effects; D014994:Xylose / Q000097:blood
chemical_list: D000596:Amino Acids; D018840:HSP70 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007656:Ketoglutaric Acids; D008070:Lipopolysaccharides; D014994:Xylose; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases