Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents
Background: Changes in the metabolic fingerprint of blood during child growth and development are a largely under-investigated area of research. The examination of such aspects requires a cohort of healthy children and adolescents who have been subjected to deep phenotyping, including collection of...
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description | Background: Changes in the metabolic fingerprint of blood during child growth and development are a largely under-investigated area of research. The examination of such aspects requires a cohort of healthy children and adolescents who have been subjected to deep phenotyping, including collection of biospecimens for metabolomic analysis. The present study considered whether amino acid (AA) and acylcarnitine (AC) concentrations are associated with age, sex, body mass index (BMI), and puberty during childhood and adolescence. It also investigated whether there are associations between amino acids (AAs) and acylcarnitines (ACs) and laboratory parameters of glucose and lipid metabolism, as well as liver, kidney, and thyroid parameters. Methods: A total of 3989 dried whole blood samples collected from 2191 healthy participants, aged 3 months to 18 years, from the LIFE Child cohort (Leipzig, Germany) were analyzed using liquid chromatography tandem mass spectrometry to detect levels of 23 AAs, 6 ACs, and free carnitine (C0). Age- and sex-related percentiles were estimated for each metabolite. In addition, correlations between laboratory parameters and levels of the selected AAs and ACs were calculated using hierarchical models. Results: Four different age-dependent profile types were identified for AAs and ACs. Investigating the association with puberty, we mainly identified peak metabolite levels at Tanner stages 2 to 3 in girls and stages 3 to 5 in boys. Significant correlations were observed between BMI standard deviation score (BMI-SDS) and certain metabolites, among them, branched-chain (leucine/isoleucine, valine) and aromatic (phenylalanine, tyrosine) amino acids. Most of the metabolites correlated significantly with absolute concentrations of glucose, glycated hemoglobin (HbA1c), triglycerides, cystatin C (CysC), and creatinine. After age adjustment, significant correlations were observed between most metabolites and CysC, as well as HbA1c. Conclusions: During childhood, several AA and AC levels are related to age, sex, BMI, and puberty. Moreover, our data verified known associations but also revealed new correlations between AAs/ACs and specific key markers of metabolic function. |
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The examination of such aspects requires a cohort of healthy children and adolescents who have been subjected to deep phenotyping, including collection of biospecimens for metabolomic analysis. The present study considered whether amino acid (AA) and acylcarnitine (AC) concentrations are associated with age, sex, body mass index (BMI), and puberty during childhood and adolescence. It also investigated whether there are associations between amino acids (AAs) and acylcarnitines (ACs) and laboratory parameters of glucose and lipid metabolism, as well as liver, kidney, and thyroid parameters. Methods: A total of 3989 dried whole blood samples collected from 2191 healthy participants, aged 3 months to 18 years, from the LIFE Child cohort (Leipzig, Germany) were analyzed using liquid chromatography tandem mass spectrometry to detect levels of 23 AAs, 6 ACs, and free carnitine (C0). Age- and sex-related percentiles were estimated for each metabolite. In addition, correlations between laboratory parameters and levels of the selected AAs and ACs were calculated using hierarchical models. Results: Four different age-dependent profile types were identified for AAs and ACs. Investigating the association with puberty, we mainly identified peak metabolite levels at Tanner stages 2 to 3 in girls and stages 3 to 5 in boys. Significant correlations were observed between BMI standard deviation score (BMI-SDS) and certain metabolites, among them, branched-chain (leucine/isoleucine, valine) and aromatic (phenylalanine, tyrosine) amino acids. Most of the metabolites correlated significantly with absolute concentrations of glucose, glycated hemoglobin (HbA1c), triglycerides, cystatin C (CysC), and creatinine. After age adjustment, significant correlations were observed between most metabolites and CysC, as well as HbA1c. Conclusions: During childhood, several AA and AC levels are related to age, sex, BMI, and puberty. Moreover, our data verified known associations but also revealed new correlations between AAs/ACs and specific key markers of metabolic function.</description><identifier>ISSN: 2218-1989</identifier><identifier>EISSN: 2218-1989</identifier><identifier>DOI: 10.3390/metabo10040149</identifier><identifier>PMID: 32290284</identifier><language>eng</language><publisher>BASEL: Mdpi</publisher><subject>acylcarnitines ; Adolescents ; Age ; Amino acids ; Biochemistry & Molecular Biology ; Body mass index ; Carbohydrates ; Carnitine ; Children ; Children & youth ; Creatinine ; Cystatin C ; dried blood ; Fatty acids ; Gender differences ; Glucose metabolism ; Hemoglobin ; Isoleucine ; Leucine ; Life Sciences & Biomedicine ; Lipid metabolism ; Liquid chromatography ; Mass spectroscopy ; Medical screening ; Metabolism ; Metabolites ; Metabolomics ; Pediatrics ; Phenotyping ; Phenylalanine ; Physiology ; Puberty ; Science & Technology ; Sex ; tandem mass spectrometry ; Thyroid ; Thyroid gland ; Triglycerides ; Tyrosine ; Valine</subject><ispartof>Metabolites, 2020-04, Vol.10 (4), p.149, Article 149</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>23</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000533907300002</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c484t-f24d856f492d1d86b18e25e043a9171e2ee535094255852a01112b1f07bfead33</citedby><cites>FETCH-LOGICAL-c484t-f24d856f492d1d86b18e25e043a9171e2ee535094255852a01112b1f07bfead33</cites><orcidid>0000-0003-2051-1249 ; 0000-0003-3224-3894 ; 0000-0002-5354-287X ; 0000-0001-6001-0356</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240971/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240971/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2106,2118,27933,27934,28257,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32290284$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hirschel, Josephin</creatorcontrib><creatorcontrib>Vogel, Mandy</creatorcontrib><creatorcontrib>Baber, Ronny</creatorcontrib><creatorcontrib>Garten, Antje</creatorcontrib><creatorcontrib>Beuchel, Carl</creatorcontrib><creatorcontrib>Dietz, Yvonne</creatorcontrib><creatorcontrib>Dittrich, Julia</creatorcontrib><creatorcontrib>Koerner, Antje</creatorcontrib><creatorcontrib>Kiess, Wieland</creatorcontrib><creatorcontrib>Ceglarek, Uta</creatorcontrib><title>Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents</title><title>Metabolites</title><addtitle>METABOLITES</addtitle><addtitle>Metabolites</addtitle><description>Background: Changes in the metabolic fingerprint of blood during child growth and development are a largely under-investigated area of research. The examination of such aspects requires a cohort of healthy children and adolescents who have been subjected to deep phenotyping, including collection of biospecimens for metabolomic analysis. The present study considered whether amino acid (AA) and acylcarnitine (AC) concentrations are associated with age, sex, body mass index (BMI), and puberty during childhood and adolescence. It also investigated whether there are associations between amino acids (AAs) and acylcarnitines (ACs) and laboratory parameters of glucose and lipid metabolism, as well as liver, kidney, and thyroid parameters. Methods: A total of 3989 dried whole blood samples collected from 2191 healthy participants, aged 3 months to 18 years, from the LIFE Child cohort (Leipzig, Germany) were analyzed using liquid chromatography tandem mass spectrometry to detect levels of 23 AAs, 6 ACs, and free carnitine (C0). Age- and sex-related percentiles were estimated for each metabolite. In addition, correlations between laboratory parameters and levels of the selected AAs and ACs were calculated using hierarchical models. Results: Four different age-dependent profile types were identified for AAs and ACs. Investigating the association with puberty, we mainly identified peak metabolite levels at Tanner stages 2 to 3 in girls and stages 3 to 5 in boys. Significant correlations were observed between BMI standard deviation score (BMI-SDS) and certain metabolites, among them, branched-chain (leucine/isoleucine, valine) and aromatic (phenylalanine, tyrosine) amino acids. Most of the metabolites correlated significantly with absolute concentrations of glucose, glycated hemoglobin (HbA1c), triglycerides, cystatin C (CysC), and creatinine. After age adjustment, significant correlations were observed between most metabolites and CysC, as well as HbA1c. Conclusions: During childhood, several AA and AC levels are related to age, sex, BMI, and puberty. Moreover, our data verified known associations but also revealed new correlations between AAs/ACs and specific key markers of metabolic function.</description><subject>acylcarnitines</subject><subject>Adolescents</subject><subject>Age</subject><subject>Amino acids</subject><subject>Biochemistry & Molecular Biology</subject><subject>Body mass index</subject><subject>Carbohydrates</subject><subject>Carnitine</subject><subject>Children</subject><subject>Children & youth</subject><subject>Creatinine</subject><subject>Cystatin C</subject><subject>dried blood</subject><subject>Fatty acids</subject><subject>Gender differences</subject><subject>Glucose metabolism</subject><subject>Hemoglobin</subject><subject>Isoleucine</subject><subject>Leucine</subject><subject>Life Sciences & Biomedicine</subject><subject>Lipid metabolism</subject><subject>Liquid chromatography</subject><subject>Mass spectroscopy</subject><subject>Medical screening</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Metabolomics</subject><subject>Pediatrics</subject><subject>Phenotyping</subject><subject>Phenylalanine</subject><subject>Physiology</subject><subject>Puberty</subject><subject>Science & Technology</subject><subject>Sex</subject><subject>tandem mass spectrometry</subject><subject>Thyroid</subject><subject>Thyroid gland</subject><subject>Triglycerides</subject><subject>Tyrosine</subject><subject>Valine</subject><issn>2218-1989</issn><issn>2218-1989</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkkmP0zAYhiMEYkbDXDkiS1yQaAfbsRP7gtSJWCpNBWIRx8hxPrcuiT3jOED_Az8ad6GacsIXb48fb2-WPSX4Ks8lftVDVI0nGDNMmHyQnVNKxJRIIR_ea59ll8OwxqkUmJeYPM7OckolpoKdZ78_Qaei9Q55g76tfAfouvO-RbPeOo9m2rZIudTVm06r4Gy0DtBit3Hne0AxQUuYoM_wa4KuF_MJ-jg2EOJmslt3IK1GCxW-QxiQdaha2a4N4PbmNm06aHBxeJI9Mqob4PJQX2Rf3775Ur2f3nx4N69mN1PNBItTQ1kreGGYpC1pRdEQAZQDZrmSpCRAAXjOsWSUc8GpwoQQ2hCDy8aAavP8Ipvvva1X6_o22F6FTe2VrXcDPixrFaLVHdSF1ESSgmkjFSO8UCapCQGmhSiNbJLr9d51OzY9tNt7BNWdSE9nnF3VS_-jLinDsiRJ8OIgCP5uhCHWvU3P0XXKgR-HmqafJqws2Pbcz_9B134MLj1VooRknMpCJupqT-nghyGAOR6G4Hqbm_o0N2nBs_tXOOJ_U5KAl3vgJzTeDNqC03DEUrD4Vlvm24zRRIv_pysbd_Gr_Ohi_gcWe93l</recordid><startdate>20200410</startdate><enddate>20200410</enddate><creator>Hirschel, Josephin</creator><creator>Vogel, Mandy</creator><creator>Baber, Ronny</creator><creator>Garten, Antje</creator><creator>Beuchel, Carl</creator><creator>Dietz, Yvonne</creator><creator>Dittrich, Julia</creator><creator>Koerner, Antje</creator><creator>Kiess, Wieland</creator><creator>Ceglarek, Uta</creator><general>Mdpi</general><general>MDPI AG</general><general>MDPI</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QR</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-2051-1249</orcidid><orcidid>https://orcid.org/0000-0003-3224-3894</orcidid><orcidid>https://orcid.org/0000-0002-5354-287X</orcidid><orcidid>https://orcid.org/0000-0001-6001-0356</orcidid></search><sort><creationdate>20200410</creationdate><title>Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents</title><author>Hirschel, Josephin ; Vogel, Mandy ; Baber, Ronny ; Garten, Antje ; Beuchel, Carl ; Dietz, Yvonne ; Dittrich, Julia ; Koerner, Antje ; Kiess, Wieland ; Ceglarek, Uta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-f24d856f492d1d86b18e25e043a9171e2ee535094255852a01112b1f07bfead33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>acylcarnitines</topic><topic>Adolescents</topic><topic>Age</topic><topic>Amino acids</topic><topic>Biochemistry & Molecular Biology</topic><topic>Body mass index</topic><topic>Carbohydrates</topic><topic>Carnitine</topic><topic>Children</topic><topic>Children & youth</topic><topic>Creatinine</topic><topic>Cystatin C</topic><topic>dried blood</topic><topic>Fatty acids</topic><topic>Gender differences</topic><topic>Glucose metabolism</topic><topic>Hemoglobin</topic><topic>Isoleucine</topic><topic>Leucine</topic><topic>Life Sciences & Biomedicine</topic><topic>Lipid metabolism</topic><topic>Liquid chromatography</topic><topic>Mass spectroscopy</topic><topic>Medical screening</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Metabolomics</topic><topic>Pediatrics</topic><topic>Phenotyping</topic><topic>Phenylalanine</topic><topic>Physiology</topic><topic>Puberty</topic><topic>Science & Technology</topic><topic>Sex</topic><topic>tandem mass spectrometry</topic><topic>Thyroid</topic><topic>Thyroid gland</topic><topic>Triglycerides</topic><topic>Tyrosine</topic><topic>Valine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hirschel, Josephin</creatorcontrib><creatorcontrib>Vogel, Mandy</creatorcontrib><creatorcontrib>Baber, Ronny</creatorcontrib><creatorcontrib>Garten, Antje</creatorcontrib><creatorcontrib>Beuchel, Carl</creatorcontrib><creatorcontrib>Dietz, Yvonne</creatorcontrib><creatorcontrib>Dittrich, Julia</creatorcontrib><creatorcontrib>Koerner, Antje</creatorcontrib><creatorcontrib>Kiess, Wieland</creatorcontrib><creatorcontrib>Ceglarek, Uta</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Chemoreception Abstracts</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Metabolites</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hirschel, Josephin</au><au>Vogel, Mandy</au><au>Baber, Ronny</au><au>Garten, Antje</au><au>Beuchel, Carl</au><au>Dietz, Yvonne</au><au>Dittrich, Julia</au><au>Koerner, Antje</au><au>Kiess, Wieland</au><au>Ceglarek, Uta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents</atitle><jtitle>Metabolites</jtitle><stitle>METABOLITES</stitle><addtitle>Metabolites</addtitle><date>2020-04-10</date><risdate>2020</risdate><volume>10</volume><issue>4</issue><spage>149</spage><pages>149-</pages><artnum>149</artnum><issn>2218-1989</issn><eissn>2218-1989</eissn><abstract>Background: Changes in the metabolic fingerprint of blood during child growth and development are a largely under-investigated area of research. The examination of such aspects requires a cohort of healthy children and adolescents who have been subjected to deep phenotyping, including collection of biospecimens for metabolomic analysis. The present study considered whether amino acid (AA) and acylcarnitine (AC) concentrations are associated with age, sex, body mass index (BMI), and puberty during childhood and adolescence. It also investigated whether there are associations between amino acids (AAs) and acylcarnitines (ACs) and laboratory parameters of glucose and lipid metabolism, as well as liver, kidney, and thyroid parameters. Methods: A total of 3989 dried whole blood samples collected from 2191 healthy participants, aged 3 months to 18 years, from the LIFE Child cohort (Leipzig, Germany) were analyzed using liquid chromatography tandem mass spectrometry to detect levels of 23 AAs, 6 ACs, and free carnitine (C0). Age- and sex-related percentiles were estimated for each metabolite. In addition, correlations between laboratory parameters and levels of the selected AAs and ACs were calculated using hierarchical models. Results: Four different age-dependent profile types were identified for AAs and ACs. Investigating the association with puberty, we mainly identified peak metabolite levels at Tanner stages 2 to 3 in girls and stages 3 to 5 in boys. Significant correlations were observed between BMI standard deviation score (BMI-SDS) and certain metabolites, among them, branched-chain (leucine/isoleucine, valine) and aromatic (phenylalanine, tyrosine) amino acids. Most of the metabolites correlated significantly with absolute concentrations of glucose, glycated hemoglobin (HbA1c), triglycerides, cystatin C (CysC), and creatinine. After age adjustment, significant correlations were observed between most metabolites and CysC, as well as HbA1c. Conclusions: During childhood, several AA and AC levels are related to age, sex, BMI, and puberty. Moreover, our data verified known associations but also revealed new correlations between AAs/ACs and specific key markers of metabolic function.</abstract><cop>BASEL</cop><pub>Mdpi</pub><pmid>32290284</pmid><doi>10.3390/metabo10040149</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0003-2051-1249</orcidid><orcidid>https://orcid.org/0000-0003-3224-3894</orcidid><orcidid>https://orcid.org/0000-0002-5354-287X</orcidid><orcidid>https://orcid.org/0000-0001-6001-0356</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | acylcarnitines Adolescents Age Amino acids Biochemistry & Molecular Biology Body mass index Carbohydrates Carnitine Children Children & youth Creatinine Cystatin C dried blood Fatty acids Gender differences Glucose metabolism Hemoglobin Isoleucine Leucine Life Sciences & Biomedicine Lipid metabolism Liquid chromatography Mass spectroscopy Medical screening Metabolism Metabolites Metabolomics Pediatrics Phenotyping Phenylalanine Physiology Puberty Science & Technology Sex tandem mass spectrometry Thyroid Thyroid gland Triglycerides Tyrosine Valine |
title | Relation of Whole Blood Amino Acid and Acylcarnitine Metabolome to Age, Sex, BMI, Puberty, and Metabolic Markers in Children and Adolescents |
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