High Leucine Diets Stimulate Cerebral Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model
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 stimula...
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| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0150376 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0150376</identifier><identifier>PMID: 26930301</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>3-Hydroxybutyric Acid - metabolism ; Acids ; Adipose tissue ; Amino acid sequence ; Amino acids ; Amino Acids, Branched-Chain - metabolism ; Analysis ; Animals ; Atrophy ; Biology and Life Sciences ; Brain ; Brain - metabolism ; Cardiac muscle ; Chain branching ; Chains ; Degradation ; Dehydrogenases ; Diet ; Diet - methods ; Enzymatic activity ; Enzyme activity ; Enzymes ; Female ; Food ; Health aspects ; Heart diseases ; Hogs ; Intestinal Mucosa - metabolism ; Intestine ; Isoleucine ; Isoleucine - metabolism ; Keto Acids - metabolism ; Ketone Bodies - metabolism ; Leucine ; Leucine - metabolism ; Liver ; Liver - metabolism ; Livestock ; Livestock production ; Male ; Medicine and Health Sciences ; Metabolic rate ; Metabolism ; Metabolites ; Models, Animal ; Mucosa ; Muscles ; Musculoskeletal system ; Myocardium - metabolism ; Nutrition research ; Pancreas ; Physical Sciences ; Physiological aspects ; Pigs ; Protein biosynthesis ; Protein synthesis ; Proteins ; Research and Analysis Methods ; Science ; Serotonin ; Serotonin - metabolism ; Skeletal muscle ; Studies ; Swine ; Tissues ; Tryptophan ; Valine ; Valine - metabolism</subject><ispartof>PloS one, 2016-03, Vol.11 (3), p.e0150376-e0150376</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Wessels et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2016 Wessels et al 2016 Wessels et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-a1c212be584b0e4b7e133d5b5af85cbaf479895eb334bc66c3581c75db5b424e3</citedby><cites>FETCH-LOGICAL-c692t-a1c212be584b0e4b7e133d5b5af85cbaf479895eb334bc66c3581c75db5b424e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773154/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773154/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26930301$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wessels, Anna G</creatorcontrib><creatorcontrib>Kluge, Holger</creatorcontrib><creatorcontrib>Hirche, Frank</creatorcontrib><creatorcontrib>Kiowski, Andreas</creatorcontrib><creatorcontrib>Schutkowski, Alexandra</creatorcontrib><creatorcontrib>Corrent, Etienne</creatorcontrib><creatorcontrib>Bartelt, Jörg</creatorcontrib><creatorcontrib>König, Bettina</creatorcontrib><creatorcontrib>Stangl, Gabriele I</creatorcontrib><title>High Leucine Diets Stimulate Cerebral Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.</description><subject>3-Hydroxybutyric Acid - metabolism</subject><subject>Acids</subject><subject>Adipose tissue</subject><subject>Amino acid sequence</subject><subject>Amino acids</subject><subject>Amino Acids, Branched-Chain - metabolism</subject><subject>Analysis</subject><subject>Animals</subject><subject>Atrophy</subject><subject>Biology and Life Sciences</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>Cardiac muscle</subject><subject>Chain branching</subject><subject>Chains</subject><subject>Degradation</subject><subject>Dehydrogenases</subject><subject>Diet</subject><subject>Diet - methods</subject><subject>Enzymatic activity</subject><subject>Enzyme activity</subject><subject>Enzymes</subject><subject>Female</subject><subject>Food</subject><subject>Health aspects</subject><subject>Heart diseases</subject><subject>Hogs</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Intestine</subject><subject>Isoleucine</subject><subject>Isoleucine - metabolism</subject><subject>Keto Acids - metabolism</subject><subject>Ketone Bodies - metabolism</subject><subject>Leucine</subject><subject>Leucine - metabolism</subject><subject>Liver</subject><subject>Liver - metabolism</subject><subject>Livestock</subject><subject>Livestock production</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Metabolic rate</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Models, Animal</subject><subject>Mucosa</subject><subject>Muscles</subject><subject>Musculoskeletal system</subject><subject>Myocardium - metabolism</subject><subject>Nutrition research</subject><subject>Pancreas</subject><subject>Physical Sciences</subject><subject>Physiological aspects</subject><subject>Pigs</subject><subject>Protein biosynthesis</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Science</subject><subject>Serotonin</subject><subject>Serotonin - metabolism</subject><subject>Skeletal muscle</subject><subject>Studies</subject><subject>Swine</subject><subject>Tissues</subject><subject>Tryptophan</subject><subject>Valine</subject><subject>Valine - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk8-O0zAQxiMEYpfCGyCwhITg0BLHdpxcVup2ga0oWkSBq2U7k9RVahc7QfQleGbcP7tq0R6QD7Ymv--bzNiTJM9xOsKE43dL13sr29HaWRilmKWE5w-Sc1ySbJhnKXl4dD5LnoSwTFNGijx_nJxleUlSkuLz5M-1aRZoBr02FtCVgS6geWdWfSs7QBPwoLxs0aWXVi-gGk4W0lg0Xhnr0FibCl1B42UlO-MskrZCn11l6g2ag3eds2Yf_ATxDOjSVRs0cVaD7fxOEtCWQF9MsxVC-zR5VMs2wLPDPki-f3j_bXI9nN18nE7Gs6HOy6wbSqwznClgBVUpUMUBE1IxxWRdMK1kTXlZlAwUIVTpPNeEFVhzVimmaEaBDJKXe99164I4tDIIzPMyJ5yRMhLTPVE5uRRrb1bSb4STRuwCzjdC-s7oFkTMqgvOGMtyRkGVCktZMpZyVtScUhy9Lg7ZerWCal9-e2J6-sWahWjcL0E5J5jRaPDmYODdzx5CJ1YmaGhbacH12__maYYLnOURffUPen91B6qRsQBjaxfz6q2pGFNKeUGy-EAGyegeKq4KVkbHG61NjJ8I3p4IItPB766RfQhiOv_6_-zNj1P29RG7ANl2i-DafveETkG6B7V3IXio75qMU7Edm9tuiO3YiMPYRNmL4wu6E93OCfkL9CoR9Q</recordid><startdate>20160301</startdate><enddate>20160301</enddate><creator>Wessels, Anna G</creator><creator>Kluge, Holger</creator><creator>Hirche, Frank</creator><creator>Kiowski, Andreas</creator><creator>Schutkowski, Alexandra</creator><creator>Corrent, Etienne</creator><creator>Bartelt, Jörg</creator><creator>König, Bettina</creator><creator>Stangl, Gabriele I</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20160301</creationdate><title>High Leucine Diets Stimulate Cerebral Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model</title><author>Wessels, Anna G ; Kluge, Holger ; Hirche, Frank ; Kiowski, Andreas ; Schutkowski, Alexandra ; Corrent, Etienne ; Bartelt, Jörg ; König, Bettina ; Stangl, Gabriele I</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-a1c212be584b0e4b7e133d5b5af85cbaf479895eb334bc66c3581c75db5b424e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>3-Hydroxybutyric Acid - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wessels, Anna G</au><au>Kluge, Holger</au><au>Hirche, Frank</au><au>Kiowski, Andreas</au><au>Schutkowski, Alexandra</au><au>Corrent, Etienne</au><au>Bartelt, Jörg</au><au>König, Bettina</au><au>Stangl, Gabriele I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High Leucine Diets Stimulate Cerebral Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-03-01</date><risdate>2016</risdate><volume>11</volume><issue>3</issue><spage>e0150376</spage><epage>e0150376</epage><pages>e0150376-e0150376</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26930301</pmid><doi>10.1371/journal.pone.0150376</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-03, Vol.11 (3), p.e0150376-e0150376 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1769637539 |
| source | MEDLINE; Public Library of Science; Full-Text Journals in Chemistry (Open access); DOAJ Directory of Open Access Journals; PubMed Central; EZB Electronic Journals Library |
| subjects | 3-Hydroxybutyric Acid - metabolism Acids Adipose tissue Amino acid sequence Amino acids Amino Acids, Branched-Chain - metabolism Analysis Animals Atrophy Biology and Life Sciences Brain Brain - metabolism Cardiac muscle Chain branching Chains Degradation Dehydrogenases Diet Diet - methods Enzymatic activity Enzyme activity Enzymes Female Food Health aspects Heart diseases Hogs Intestinal Mucosa - metabolism Intestine Isoleucine Isoleucine - metabolism Keto Acids - metabolism Ketone Bodies - metabolism Leucine Leucine - metabolism Liver Liver - metabolism Livestock Livestock production Male Medicine and Health Sciences Metabolic rate Metabolism Metabolites Models, Animal Mucosa Muscles Musculoskeletal system Myocardium - metabolism Nutrition research Pancreas Physical Sciences Physiological aspects Pigs Protein biosynthesis Protein synthesis Proteins Research and Analysis Methods Science Serotonin Serotonin - metabolism Skeletal muscle Studies Swine Tissues Tryptophan Valine Valine - metabolism |
| title | High Leucine Diets Stimulate Cerebral Branched-Chain Amino Acid Degradation and Modify Serotonin and Ketone Body Concentrations in a Pig Model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T07%3A07%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20Leucine%20Diets%20Stimulate%20Cerebral%20Branched-Chain%20Amino%20Acid%20Degradation%20and%20Modify%20Serotonin%20and%20Ketone%20Body%20Concentrations%20in%20a%20Pig%20Model&rft.jtitle=PloS%20one&rft.au=Wessels,%20Anna%20G&rft.date=2016-03-01&rft.volume=11&rft.issue=3&rft.spage=e0150376&rft.epage=e0150376&rft.pages=e0150376-e0150376&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0150376&rft_dat=%3Cgale_plos_%3EA444783230%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1769637539&rft_id=info:pmid/26930301&rft_galeid=A444783230&rft_doaj_id=oai_doaj_org_article_5afc875552654eb9b1aa9550758f7441&rfr_iscdi=true |