{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:35:18Z","timestamp":1787168118831,"version":"build-2736575974"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Evidence, albeit with conflicting results, has suggested that cardiometabolic risk factors, including obesity, type 2 diabetes (T2D), dyslipidemia, and hypertension, are highly associated with changes in metabolic signature, especially plasma amino acids and acylcarnitines levels. Here, we aimed to evaluate the association of circulating levels of amino acids and acylcarnitines with metabolic syndrome (MetS) and its components in Iranian adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This cross-sectional study was performed on 1192 participants from the large\u2013scale cross-sectional study of Surveillance of Risk Factors of non-communicable diseases (NCDs) in Iran (STEP 2016). The circulating levels of amino acids and acylcarnitines were measured using liquid chromatography-tandem mass spectrometry (LC-MS\/MS) in individuals with MetS (n=529) and without MetS (n=663).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The higher plasma levels of branched-chain amino acids (Val, Leu), aromatic amino acids (Phe, Tyr), Pro, Ala, Glu, and the ratio of Asp to Asn were significantly associated with MetS, whereas lower circulating levels of Gly, Ser, His, Asn, and citrulline were significantly associated with MetS. As for plasma levels of free carnitine and acylcarnitines, higher levels of short-chain acylcarnitines (C2, C3, C4DC), free carnitine (C0), and long-chain acylcarnitines (C16, C18OH) were significantly associated with MetS. Principal component analysis (PCA) showed that factor 3 (Tyr, Leu, Val, Met, Trp, Phe, Thr) [OR:1.165, 95% CI: 1.121-1.210, P&amp;lt;0.001], factor 7 (C0, C3, C4) [OR:1.257, 95% CI: 1.150-1.374, P&amp;lt;0.001], factor 8 (Gly, Ser) [OR:0.718, 95% CI: 0.651-0.793, P&amp;lt; 0.001], factor 9 (Ala, Pro, C4DC) [OR:1.883, 95% CI: 1.669-2.124, P&amp;lt;0.001], factor 10 (Glu, Asp, C18:2OH) [OR:1.132, 95% CI: 1.032-1.242, P= 0.009], factor 11 (citrulline, ornithine) [OR:0.862, 95% CI: 0.778-0.955, P= 0.004] and 13 (C18OH, C18:1 OH) [OR: 1.242, 95% CI: 1.042-1.480, P= 0.016] were independently correlated with metabolic syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Change in amino acid, and acylcarnitines profiles were seen in patients with MetS. Moreover, the alteration in the circulating levels of amino acids and acylcarnitines is along with an increase in MetS component number. It also seems that amino acid and acylcarnitines profiles can provide valuable information on evaluating and monitoring MetS risk. However, further studies are needed to establish this concept.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2023.1058952","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:49:50Z","timestamp":1677458990000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["The association between acylcarnitine and amino acids profile and metabolic syndrome and its components in Iranian adults: Data from STEPs 2016"],"prefix":"10.3389","volume":"14","author":[{"given":"Hananeh","family":"Taghizadeh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Solaleh","family":"Emamgholipour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaghayegh","family":"Hosseinkhani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Babak","family":"Arjmand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negar","family":"Rezaei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arezou","family":"Dilmaghani-Marand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erfan","family":"Ghasemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nekoo","family":"Panahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hojat","family":"Dehghanbanadaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robabeh","family":"Ghodssi-Ghassemabadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niloufar","family":"Najjar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mojgan","family":"Asadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"khoshniat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bagher","family":"Larijani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farideh","family":"Razi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.5223\/pghn.2020.23.3.189","article-title":"Novel insights into the pathogenesis and management of the metabolic syndrome","volume":"23","author":"Wang","year":"2020","journal-title":"Pediatr gastroenterology Hepatol Nutr"},{"key":"B2","unstructured":"The IDF consensus worldwide definition of the metabolic syndrome2006"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0241926","article-title":"A nationwide study of metabolic syndrome prevalence in iran; a comparative analysis of six definitions","volume":"16","author":"Tabatabaei-Malazy","year":"2021","journal-title":"PLos One"},{"key":"B4","doi-asserted-by":"publisher","first-page":"23","DOI":"10.4239\/wjd.v10.i1.23","article-title":"Exploratory metabolomics of metabolic syndrome: A status report","volume":"10","author":"Lent-Schochet","year":"2019","journal-title":"World J diabetes."},{"key":"B5","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/s41598-019-56909-7","article-title":"Metabolomic and lipidomic signatures of metabolic syndrome and its physiological components in adults: A systematic review","volume":"10","author":"Monnerie","year":"2020","journal-title":"Sci Rep"},{"key":"B6","doi-asserted-by":"publisher","first-page":"806","DOI":"10.3390\/nu12030806","article-title":"Detection of early disease risk factors associated with metabolic syndrome: A new era with the NMR metabolomics assessment","volume":"12","author":"Hernandez-Baixauli","year":"2020","journal-title":"Nutrients."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1159\/000345759","article-title":"Similarities in serum acylcarnitine patterns in type 1 and type 2 diabetes mellitus and in metabolic syndrome","volume":"62","author":"Bene","year":"2013","journal-title":"Ann Nutr Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.P088005","article-title":"Erythrocyte PUFAs, circulating acylcarnitines, and metabolic syndrome risk: A prospective study in Chinese","volume":"60","author":"Ma","year":"2019","journal-title":"J Lipid Res"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082459","article-title":"Serum levels of acylcarnitines are altered in prediabetic conditions","volume":"8","author":"Mai","year":"2013","journal-title":"PLos One"},{"key":"B10","doi-asserted-by":"publisher","first-page":"17528","DOI":"10.1038\/s41598-017-17797-x","article-title":"Plasma acylcarnitine concentrations reflect the acylcarnitine profile in cardiac tissues","volume":"7","author":"Makrecka-Kuka","year":"2017","journal-title":"Sci Rep"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2017.07.006","article-title":"Amino acid profile and metabolic syndrome in a male Mediterranean population: A cross-sectional study","volume":"27","author":"Ntzouvani","year":"2017","journal-title":"Nutrition metabolism Cardiovasc Dis NMCD."},{"key":"B12","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.diabres.2017.07.023","article-title":"Abnormal circulating amino acid profiles in multiple metabolic disorders","volume":"132","author":"Okekunle","year":"2017","journal-title":"Diabetes Res Clin practice."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2018.05.014","article-title":"Exploratory lipidomics in patients with nascent metabolic syndrome","volume":"32","author":"Ramakrishanan","year":"2018","journal-title":"J Diabetes its Complications."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19040954","article-title":"Branched chain amino acids: Beyond nutrition metabolism","volume":"19","author":"Nie","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.11R05FM","article-title":"New therapeutic strategy for amino acid medicine: notable functions of branched chain amino acids as biological regulators","volume":"118","author":"Yoshizawa","year":"2012","journal-title":"J Pharmacol Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs424","article-title":"A diabetes-predictive amino acid score and future cardiovascular disease","volume":"34","author":"Magnusson","year":"2013","journal-title":"Eur Heart J"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2307","article-title":"Metabolite profiles and the risk of developing diabetes","volume":"17","author":"Wang","year":"2011","journal-title":"Nat Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"11918","DOI":"10.1038\/srep11918","article-title":"Plasma free amino acid profiles predict four-year risk of developing diabetes, metabolic syndrome, dyslipidemia, and hypertension in Japanese population","volume":"5","author":"Yamakado","year":"2015","journal-title":"Sci Rep"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2011.10.008","article-title":"The mitochondrial carnitine\/acylcarnitine carrier: function, structure and physiopathology","volume":"32","author":"Indiveri","year":"2011","journal-title":"Mol aspects Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e5410","DOI":"10.7717\/peerj.5410","article-title":"Metabolomic analysis of obesity, metabolic syndrome, and type 2 diabetes: amino acid and acylcarnitine levels change along a spectrum of metabolic wellness","volume":"6","author":"Libert","year":"2018","journal-title":"PeerJ."},{"key":"B21","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.cmet.2016.09.018","article-title":"Metabolomics and metabolic diseases: Where do we stand","volume":"25","author":"Newgard","year":"2017","journal-title":"Cell Metab"},{"key":"B22","article-title":"Protocol design for large\u2013scale cross\u2013sectional studies of surveillance of risk factors of non\u2013communicable diseases in Iran: STEPs 2016","volume":"20","author":"Djalalinia","year":"2017","journal-title":"Arch Iranian Med"},{"key":"B23","volume-title":"Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatment panel III): The program. Circulation","year":"2002"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s40200-021-00786-3","article-title":"Mass spectrometry with derivatization method for concurrent measurement of amino acids and acylcarnitines in plasma of diabetic type 2 patients with diabetic nephropathy","volume":"20","author":"Esmati","year":"2021","journal-title":"J Diabetes Metab Disord"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-020-02884-7","article-title":"Analytical methods for amino acid determination in organisms","volume":"52","author":"Xu","year":"2020","journal-title":"Amino Acids"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-00990-1","article-title":"Laboratory analysis of acylcarnitines, 2020 update: a technical standard of the American college of medical genetics and genomics (ACMG)","volume":"23","author":"Miller","year":"2021","journal-title":"Genet Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2015.0126","article-title":"A metabolomic approach to understanding the metabolic link between obesity and diabetes","volume":"38","author":"Park","year":"2015","journal-title":"Molecules Cells"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1039\/C6RA28715H","article-title":"Emerging role and recent applications of metabolomics biomarkers in obesity disease research","volume":"7","author":"Zhang","year":"2017","journal-title":"Rsc Advances."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.795044","article-title":"Metabolic syndrome and its components are associated with altered amino acid profile in Chinese han population","volume":"12","author":"Sun","year":"2021","journal-title":"Front endocrinology."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-016-2182-7","article-title":"Quantitative proteomics analysis reveals glutamine deprivation activates fatty acid \u03b2-oxidation pathway in HepG2 cells","volume":"48","author":"Long","year":"2016","journal-title":"Amino Acids"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1039\/D0FO02364G","article-title":"Dietary supplementation with aromatic amino acids decreased triglycerides and alleviated hepatic steatosis by stimulating bile acid synthesis in mice","volume":"12","author":"Ma","year":"2021","journal-title":"Food Funct"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-017-2494-2","article-title":"The role of methionine on metabolism, oxidative stress, and diseases","volume":"49","author":"Mart\u00ednez","year":"2017","journal-title":"Amino Acids"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-021-03051-2","article-title":"Proline metabolism and redox; Maintaining a balance in health and disease","volume":"53","author":"Vettore","year":"2021","journal-title":"Amino Acids"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201700951","article-title":"Metabolic regulation of methionine restriction in diabetes","volume":"62","author":"Yin","year":"2018","journal-title":"Mol Nutr Food Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/nu11061356","article-title":"Glycine metabolism and its alterations in obesity and metabolic diseases","volume":"11","author":"Alves","year":"2019","journal-title":"Nutrients."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/nu12030848","article-title":"Histidine in health and disease: Metabolism, physiological importance, and use as a supplement","volume":"12","author":"Hole\u010dek","year":"2020","journal-title":"Nutrients"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.067827","article-title":"Metabolite profiling identifies pathways associated with metabolic risk in humans","volume":"125","author":"Cheng","year":"2012","journal-title":"Circulation."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0895","article-title":"Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults","volume":"36","author":"W\u00fcrtz","year":"2013","journal-title":"Diabetes Care"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-022-11970-7","article-title":"Targeted metabolomics analysis of amino acids and acylcarnitines as risk markers for diabetes by LC\u2013MS\/MS technique","volume":"12","author":"Hosseinkhani","year":"2022","journal-title":"Sci Rep"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-10-0150","article-title":"Lifestyle modification in metabolic syndrome and associated changes in plasma amino acid profiles","volume":"74","author":"Kamaura","year":"2010","journal-title":"Circ J"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3976","article-title":"Production and release of acylcarnitines by primary myotubes reflect the differences in fasting fat oxidation of the donors","volume":"98","author":"Wolf","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B42","volume-title":"The respiratory quotient (RQ)","author":"Nestle","year":"2012"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2014.04.013","article-title":"Human serum acylcarnitine profiles in different glucose tolerance states","volume":"104","author":"Zhang","year":"2014","journal-title":"Diabetes Res Clin Pract"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2009.510","article-title":"Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity","volume":"18","author":"Mihalik","year":"2010","journal-title":"Obes (Silver Spring Md)."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1016\/j.fertnstert.2012.08.024","article-title":"Free carnitine and acylcarnitines in obese patients with polycystic ovary syndrome and effects of pioglitazone treatment","volume":"98","author":"Vigerust","year":"2012","journal-title":"Fertility sterility."},{"key":"B46","doi-asserted-by":"publisher","first-page":"8418","DOI":"10.1038\/s41598-022-11970-7","article-title":"Targeted metabolomics analysis of amino acids and acylcarnitines as risk markers for diabetes by LC-MS\/MS technique","volume":"12","author":"Hosseinkhani","year":"2022","journal-title":"Sci Rep"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002215","article-title":"Discovery of sexual dimorphisms in metabolic and genetic biomarkers","volume":"7","author":"Mittelstrass","year":"2011","journal-title":"PLos Genet"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-015-0829-0","article-title":"Gender-specific pathway differences in the human serum metabolome","volume":"11","author":"Krumsiek","year":"2015","journal-title":"Metabolomics Off J Metabolomic Society."},{"key":"B49","doi-asserted-by":"publisher","first-page":"e0183228","DOI":"10.1371\/journal.pone.0183228","article-title":"Metabolite patterns predicting sex and age in participants of the karlsruhe metabolomics and nutrition (KarMeN) study","volume":"12","author":"Rist","year":"2017","journal-title":"PLos One"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1021\/pr500434s","article-title":"The metabolite profiles of the obese population are gender-dependent","volume":"13","author":"Xie","year":"2014","journal-title":"J Proteome Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1058952\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:49:56Z","timestamp":1677458996000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1058952\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,27]]},"references-count":50,"alternative-id":["10.3389\/fendo.2023.1058952"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1058952","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,27]]},"article-number":"1058952"}}