title: High Leucine Diets Stimulate Cerebral Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model.
abstract: In addition to its role as an essential protein component, leucine (Leu) displays several other metabolic functions such as activation of protein synthesis. This property makes it an interesting amino acid for the therapy of human muscle atrophy and for livestock production. However, Leu can stimulate its own degradation via the branched-chain keto acid dehydrogenase complex (BCKDH). To examine the response of several tissues to excessive Leu, pigs were fed diets containing two- (L2) and four-fold (L4) higher Leu contents than the recommended amount (control). We found that the L4 diet led to a pronounced increase in BCKDH activity in the brain (2.5-fold, P < 0.05), liver (1.8-fold, P < 0.05) and cardiac muscle (1.7-fold, P < 0.05), whereas we found no changes in enzyme activity in the pancreas, skeletal muscle, adipose tissue and intestinal mucosa. The L2 diet had only weak effects on BCKDH activity. Both high Leu diets reduced the concentrations of free valine and isoleucine in nearly all tissues. In the brain, high Leu diets modified the amount of tryptophan available: for serotonin synthesis. Compared to the controls, pigs treated with the high Leu diets consumed less food, showed increased plasma concentrations of 3-hydroxybutyrate and reduced levels of circulating serotonin. In conclusion, excessive Leu can stimulate BCKDH activity in several tissues, including the brain. Changes in cerebral tryptophan, along with the changes in amino acid-derived metabolites in the plasma may limit the use of high Leu diets to treat muscle atrophy or to increase muscle growth.
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Wessels
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Kluge
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Hirche
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kiowski
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schutkowski
authors.affiliation: AJINOMOTO EUROLYSINE S.A.S., 75817, Paris Cedex 17, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Corrent
authors.affiliation: Lohmann Animal Nutrition GmbH, 27472, Cuxhaven, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Bartelt
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: König
authors.affiliation: Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany.
authors.forename: Gabriele I
authors.initials: GI
authors.lastname: Stangl
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004032:Diet / Q000379:methods; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D007532:Isoleucine / Q000378:metabolism; D007651:Keto Acids / Q000378:metabolism; D007657:Ketone Bodies / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013552:Swine; D014633:Valine / Q000378:metabolism
chemical_list: D000597:Amino Acids, Branched-Chain; D007651:Keto Acids; D007657:Ketone Bodies; D007532:Isoleucine; D012701:Serotonin; D007930:Leucine; D014633:Valine; D020155:3-Hydroxybutyric Acid