{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:48:58Z","timestamp":1789620538098,"version":"build-2803163510"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Breeding and Extension Technology System of High Efficiency Mutton Sheep in Xinjiang Uygur Autonomous Region","award":["xjnqry-g-2021"],"award-info":[{"award-number":["xjnqry-g-2021"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Guanidinoacetic acid (GAA) is the only precursor for the creatine synthesis of vertebrates. Creatine (Cr) and phosphocreatine (PCr) are able to provide energy for the rapid growth and development of the muscle tissue. This study evaluated the effects of dietary different levels GAA on growth performance, GAA absorption and creatine metabolism of lambs. Twenty-four 3-month-old healthy Kazakh male lambs (body weight = 27.35\u00b1 0.58 kg) were randomly divided into four groups with 6 lambs in each group. The lambs were fed with the basal diets supplemented with 0 (0 mg\/kg group), 500 (500 mg\/kg group), 1000 (1000 mg\/kg group) and 1500 mg (1500 mg\/kg group) GAA per kg diet (DM basis), respectively. The results showed that, as the GAA content of the diet increased, there was a quadratic change in DMI, with the lowest in the 500 mg\/kg group and the highest in the 0 mg\/kg group. The CK enzyme activity and ATP content in quadriceps muscle increased linearly with increasing levels of diary GAA in the diet. PCr levels and ADP levels in the longest dorsal muscle increased linearly with increasing levels of GAA in the diet. The relative expression of <jats:italic>SLC6A6<\/jats:italic> and <jats:italic>SLC6A8<\/jats:italic> mRNA in the jejunum and ileum mucosa showed a quadratic change as the dietary GAA level increased, with the lowest relative expression in both the 1500 mg\/kg group. With the increase of dietary GAA level, both Cr concentration in hepatic vein plasma and the portal plasma GAA concentration shows a quadratic change, with the highest concentration in the 500 mg\/kg group and the lowest concentration in the 0 mg\/kg group. Therefore, dietary supplementation with 500~1000 mg\/kg DM GAA is recommended for lambs.<\/jats:p>","DOI":"10.1371\/journal.pone.0264864","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T18:35:25Z","timestamp":1647023725000},"page":"e0264864","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":26,"title":["Effects of dietary guanidinoacetic acid on growth performance, guanidinoacetic acid absorption and creatine metabolism of lambs"],"prefix":"10.1371","volume":"17","author":[{"given":"Shiqi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjiang","family":"Zang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caidie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0815-6419","authenticated-orcid":true,"given":"Kailun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,11]]},"reference":[{"issue":"4","key":"pone.0264864.ref001","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1017\/S0043933908000160","article-title":"Important metabolic pathways in poultry embryos prior to hatch","volume":"64","author":"J Oliveira","year":"2008","journal-title":"World\u2019s Poult Sci J"},{"issue":"12","key":"pone.0264864.ref002","first-page":"1273","article-title":"Creatine Supplementation and Skeletal Muscle Metabolism for Building Muscle Mass- Review of the Potential Mechanisms of Action","volume":"18","author":"F Farshidfar","year":"2017","journal-title":"Arch Biochem Biophys"},{"issue":"3","key":"pone.0264864.ref003","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1152\/physrev.2000.80.3.1107","article-title":"Creatine and Creatinine Metabolism","volume":"80","author":"W Markus","year":"2000","journal-title":"Physiol Rev"},{"key":"pone.0264864.ref004","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/pr.2017.208","article-title":"Bertolo RF; Brunton JA. Creatine supplementation to total parenteral nutrition improves creatine status and supports greater liver and kidney protein synthesis in neonatal piglets","volume":"83","author":"CO Dinesh","year":"2018","journal-title":"Pediatr Res"},{"key":"pone.0264864.ref005","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.anifeedsci.2015.03.010","article-title":"Effects of dietary supplementation of guanidinoacetic acid and combination of guanidinoacetic acid and betaine on postmortem glycolysis and meat quality of finishing pigs","volume":"205","author":"Y Liu","year":"2015","journal-title":"Anim Feed Sci Technol"},{"key":"pone.0264864.ref006","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1093\/jas\/sky137","article-title":"Supplementation of guanidinoacetic acid to pig diets: effects on performance, carcass characteristics, and meat quality","volume":"96","author":"B Jayaraman","year":"2018","journal-title":"J Anim Sci"},{"issue":"3","key":"pone.0264864.ref007","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.5433\/1679-0359.2018v39n3p1307","article-title":"Effect of supplementation of guanidinoacetic acid and arginine in vegetable diets for broiler on performance, carcass yield and meat quality","volume":"39","author":"A Esser","year":"2018","journal-title":"Semina Cienc Agrar"},{"issue":"8","key":"pone.0264864.ref008","doi-asserted-by":"crossref","first-page":"3223","DOI":"10.3382\/ps\/pez052","article-title":"Attenuating effects of guanidinoacetic acid on preslaughter transport-induced muscle energy expenditure and rapid glycolysis of broilers","volume":"98","author":"L Zhang","year":"2019","journal-title":"Poult Sci"},{"issue":"4","key":"pone.0264864.ref009","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1080\/00071668.2018.1476678","article-title":"Guanidinoacetic acid supplementation in broiler chickens fed on corn-soybean diets affects performance in the finisher period and energy metabolites in breast muscle independent of diet nutrient density","volume":"59","author":"M Majdeddin","year":"2018","journal-title":"Br Poult Sci"},{"issue":"12","key":"pone.0264864.ref010","doi-asserted-by":"crossref","first-page":"2535","DOI":"10.1017\/S1751731120001603","article-title":"Effects of guanidinoacetic acid supplementation on growth performance, nutrient digestion, rumen fermentation and blood metabolites in Angus bulls\u2014ScienceDirect","volume":"14","author":"SY Li","year":"2020","journal-title":"Anim"},{"issue":"2","key":"pone.0264864.ref011","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/0005-2728(92)90096-K","article-title":"Mitochondrial creatine kinase: a key enzyme of aerobic energy metabolism","volume":"1102","author":"M Wyss","year":"1992","journal-title":"Biochim Biophys Acta Bioenerg"},{"issue":"2","key":"pone.0264864.ref012","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/BF00585149","article-title":"The time course of phosphorylcreatine resynthesis during recovery of the quadriceps muscle in man","volume":"367","author":"RC Harris","year":"1976","journal-title":"Pfluegers Arch."},{"issue":"2","key":"pone.0264864.ref013","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1111\/j.1471-4159.2009.06332.x","article-title":"The blood\u2013brain barrier transport and cerebral distribution of guanidinoacetate in rats: involvement of creatine and taurine transporters","volume":"111","author":"T Masanori","year":"2009","journal-title":"J Neurochem"},{"issue":"4","key":"pone.0264864.ref014","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s10545-011-9433-2","article-title":"Creatine and guanidinoacetate transport at blood-brain and blood-cerebrospinal fluid barriers.","volume":"35","author":"O Braissant","year":"2012","journal-title":"J. Inherited Metab Dis"},{"issue":"3","key":"pone.0264864.ref015","first-page":"127","article-title":"Ontogeny regulates creatine metabolism in rat small and large intestine","volume":"60","author":"P Garcia-Miranda","year":"2009","journal-title":"J Physiol Pharmacol"},{"issue":"1 Pt 1","key":"pone.0264864.ref016","doi-asserted-by":"crossref","first-page":"C128","DOI":"10.1152\/ajpcell.1986.251.1.C128","article-title":"Creatine uptake, metabolism, and efflux in human monocytes and macrophages","volume":"251","author":"JD Loike","year":"1986","journal-title":"Am J Physiol"},{"issue":"1","key":"pone.0264864.ref017","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1006\/abbi.1998.0959","article-title":"Molecular characterization of the human CRT-1 creatine transporter expressed in Xenopus oocytes","volume":"361","author":"W Dai","year":"1999","journal-title":"Arch Biochem Biophys"},{"issue":"6","key":"pone.0264864.ref018","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1139\/h04-045","article-title":"Elevation of creatine in red blood cells in vegetarians and nonvegetarians after creatine supplementation","volume":"29","author":"VM Maccormick","year":"2004","journal-title":"Can J Appl Physiol"},{"key":"pone.0264864.ref019","volume-title":"Nutrient requirements of small ruminants: sheep, goats, cervids, and new world camelids","author":"NRC (National Research Council)","year":"2007"},{"key":"pone.0264864.ref020","doi-asserted-by":"crossref","first-page":"5275","DOI":"10.3390\/molecules26175275","article-title":"Effects of Duodenal 5-Hydroxytryptophan Perfusion on Melatonin Synthesis in GI Tract of Sheep","volume":"26","author":"J Pan","year":"2021","journal-title":"Molecules"},{"key":"pone.0264864.ref021","volume-title":"Methods of Analysis","author":"Association of Official Analytical Chemists (AOAC).","year":"1990","edition":"15"},{"key":"pone.0264864.ref022","doi-asserted-by":"crossref","first-page":"3583","DOI":"10.3168\/jds.S0022-0302(91)78551-2","article-title":"Methods for dietary fiber, neutral detergent fifiber and non-starch polysaccharides in relation to animal nutrition","volume":"74","author":"PJ Van Soest","year":"1991","journal-title":"J Dairy Sci"},{"key":"pone.0264864.ref023","first-page":"1","volume-title":"Forage fifiber analysis. Agricultural handbook.","author":"HK Goering","year":"1970"},{"key":"pone.0264864.ref024","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s00726-011-1146-1","article-title":"A simple screening method using ion chromatography for the diagnosis of cerebral creatine deficiency syndromes[J]","volume":"43","author":"T Wada","year":"2012","journal-title":"Amino Acids"},{"key":"pone.0264864.ref025","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.3945\/jn.116.236000","article-title":"Dietary Supplementation with \u03b1-Ketoglutarate Activates mTOR Signaling and Enhances Energy Status in Skeletal Muscle of Lipopolysaccharide-Challenged Piglets","volume":"146","author":"L Wang","year":"2016","journal-title":"J Nutr"},{"key":"pone.0264864.ref026","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data using Real-Time Quantitative PCR","volume":"25","author":"KJ Livak","year":"2002","journal-title":"Method"},{"key":"pone.0264864.ref027","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1042\/bj2810021","article-title":"Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the \u2019phosphocreatine circuit\u2019 for cellular energy homeostasis","volume":"281","author":"T Wallimann","year":"1992","journal-title":"Biochem J"},{"key":"pone.0264864.ref028","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1023\/A:1011908606819","article-title":"Creatine and the creatine transporter: A review","volume":"224","author":"RJ Snow","year":"2001","journal-title":"Mol Cell Biochem"},{"key":"pone.0264864.ref029","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1152\/physrev.2000.80.3.1107","article-title":"Creatine and creatinine metabolism","volume":"80","author":"M Wyss","year":"2000","journal-title":"Physiol Rev"},{"key":"pone.0264864.ref030","doi-asserted-by":"crossref","first-page":"37361","DOI":"10.1074\/jbc.M604123200","article-title":"Mitochondrial creatine kinase activity prevents reactive oxygen species generation antioxidant role of mitochondrial kinase-dependent ADP re-cycling activity","volume":"281","author":"LE Meyer","year":"2006","journal-title":"J Biol Chem"},{"key":"pone.0264864.ref031","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.nut.2015.11.006","article-title":"Guanidinoacetic acid increases skeletal muscle creatine stores in healthy men","volume":"32","author":"SM Ostojic","year":"2016","journal-title":"Nutrition"},{"key":"pone.0264864.ref032","first-page":"435","article-title":"Effects of supplementing broiler diets with CreAMINO on broiler performance, carcass traits and the expression of muscle growth related genes.","volume":"5","author":"AE Metwally","year":"2015","journal-title":"Res Opin Anim Vet Sci"},{"key":"pone.0264864.ref033","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3382\/ps.2011-01585","article-title":"Supplementation of guanidinoacetic acid to broiler diets: Effects on performance, carcass characteristics, meat quality, and energy metabolism","volume":"91","author":"J Michiels","year":"2012","journal-title":"Poult Sci"},{"key":"pone.0264864.ref034","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1111\/are.13505","article-title":"Effects of guanidinoacetic acid supplementation in all\u2010plant protein diets on growth, antioxidant capacity and muscle energy metabolism of bullfrog Rana (Lithobates) catesbeiana.","volume":"49","author":"Q.H Zeng","year":"2018","journal-title":"Aquacult. Res."},{"key":"pone.0264864.ref035","doi-asserted-by":"crossref","first-page":"3269","DOI":"10.4081\/ijas.2014.3269","article-title":"The relationship between guanidino acetic acid and metabolisable energy level of diets on performance of broiler chickens","volume":"13","author":"A.M Abudabos","year":"2014","journal-title":"Ital J Anim Sci"},{"key":"pone.0264864.ref036","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.1093\/jas\/sky186","article-title":"Effects of guanidinoacetic acid on growth performance, creatine and energy metabolism, and carcass characteristics in growing-finishing pigs","volume":"96","author":"DT He","year":"2018","journal-title":"J Anim Sci"},{"issue":"9","key":"pone.0264864.ref037","first-page":"1","article-title":"Relative bioavailability of guanidinoacetic acid delivered ruminally or abomasally to cattle.[J]","volume":"98","author":"F Speer Hannah","year":"2020","journal-title":"J Anim Sci"},{"key":"pone.0264864.ref038","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/0003-9861(83)90293-X","article-title":"Guanidoacetate methyltransferase from rat liver: purification, properties, and evidence for the involvement of sulfhydryl groups for activity","volume":"226","author":"H Ogawa","year":"1983","journal-title":"Arch Biochem Biophys"},{"key":"pone.0264864.ref039","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ymgme.2004.05.001","article-title":"Creatine and guanidinoacetate: diagnostic markers for inborn errors in creatine biosynthesis and transport","volume":"82","author":"LS Almeida","year":"2004","journal-title":"Mol Genet Metab"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264864","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T18:36:03Z","timestamp":1647023763000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0264864"}},"subtitle":[],"editor":[{"given":"Juan J.","family":"Loor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,3,11]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0264864","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,11]]}}}