Amino Acid Metabolism is Altered in Adolescents with Nonalcoholic Fatty Liver Disease—An Untargeted, High Resolution Metabolomics Study
Objective To conduct an untargeted, high resolution exploration of metabolic pathways that was altered in association with hepatic steatosis in adolescents. Study design This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17 years evaluated for hepatic steat...
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| Veröffentlicht in: | The Journal of pediatrics 2016-05, Vol.172, p.14-19.e5 |
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| container_title | The Journal of pediatrics |
| container_volume | 172 |
| creator | Jin, Ran, PhD Banton, Sophia, MS, MPH Tran, ViLinh T., PhD Konomi, Juna V., PhD Li, Shuzhao, PhD Jones, Dean P., PhD Vos, Miriam B., MD, MSPH |
| description | Objective To conduct an untargeted, high resolution exploration of metabolic pathways that was altered in association with hepatic steatosis in adolescents. Study design This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17 years evaluated for hepatic steatosis using magnetic resonance spectroscopy. Of these 39 individuals, 30 had hepatic steatosis ≥5% and 9 were matched controls with hepatic steatosis |
| doi_str_mv | 10.1016/j.jpeds.2016.01.026 |
| format | Article |
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Study design This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17 years evaluated for hepatic steatosis using magnetic resonance spectroscopy. Of these 39 individuals, 30 had hepatic steatosis ≥5% and 9 were matched controls with hepatic steatosis <5%. Fasting plasma samples were analyzed in triplicate using ultra-high resolution metabolomics on a Thermo Fisher Q Exactive mass spectrometry system, coupled with C18 reverse phase liquid chromatography. Differences in plasma metabolites between adolescents with and without nonalcoholic fatty liver disease (NAFLD) were determined by independent t tests and visualized using Manhattan plots. Untargeted pathway analyses using Mummichog were performed among the significant metabolites to identify pathways that were most dysregulated in NAFLD. Results The metabolomics analysis yielded 9583 metabolites, and 7711 with 80% presence across all samples remained for statistical testing. Of these, 478 metabolites were associated with the presence of NAFLD compared with the matched controls. Pathway analysis revealed that along with lipid metabolism, several major amino acid pathways were dysregulated in NAFLD, with tyrosine metabolism being the most affected. Conclusions Metabolic pathways of several amino acids are significantly disturbed in adolescents with elevated hepatic steatosis. This is a novel finding and suggests that these pathways may be integral in the mechanisms of NAFLD.</description><identifier>ISSN: 0022-3476</identifier><identifier>EISSN: 1097-6833</identifier><identifier>DOI: 10.1016/j.jpeds.2016.01.026</identifier><identifier>PMID: 26858195</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Amino Acids - metabolism ; Case-Control Studies ; Child ; Female ; Humans ; Liver - pathology ; Magnetic Resonance Spectroscopy ; Male ; Metabolomics - methods ; Non-alcoholic Fatty Liver Disease - complications ; Non-alcoholic Fatty Liver Disease - metabolism ; Obesity - metabolism ; Pediatrics ; Prospective Studies</subject><ispartof>The Journal of pediatrics, 2016-05, Vol.172, p.14-19.e5</ispartof><rights>Elsevier Inc.</rights><rights>2016 Elsevier Inc.</rights><rights>Copyright © 2016 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-c82ae35231d1fec793abc91f7b32c23e7941a795d057d77d54dd47726fdc17e93</citedby><cites>FETCH-LOGICAL-c459t-c82ae35231d1fec793abc91f7b32c23e7941a795d057d77d54dd47726fdc17e93</cites><orcidid>0000-0002-9352-6380</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jpeds.2016.01.026$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26858195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jin, Ran, PhD</creatorcontrib><creatorcontrib>Banton, Sophia, MS, MPH</creatorcontrib><creatorcontrib>Tran, ViLinh T., PhD</creatorcontrib><creatorcontrib>Konomi, Juna V., PhD</creatorcontrib><creatorcontrib>Li, Shuzhao, PhD</creatorcontrib><creatorcontrib>Jones, Dean P., PhD</creatorcontrib><creatorcontrib>Vos, Miriam B., MD, MSPH</creatorcontrib><title>Amino Acid Metabolism is Altered in Adolescents with Nonalcoholic Fatty Liver Disease—An Untargeted, High Resolution Metabolomics Study</title><title>The Journal of pediatrics</title><addtitle>J Pediatr</addtitle><description>Objective To conduct an untargeted, high resolution exploration of metabolic pathways that was altered in association with hepatic steatosis in adolescents. Study design This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17 years evaluated for hepatic steatosis using magnetic resonance spectroscopy. Of these 39 individuals, 30 had hepatic steatosis ≥5% and 9 were matched controls with hepatic steatosis <5%. Fasting plasma samples were analyzed in triplicate using ultra-high resolution metabolomics on a Thermo Fisher Q Exactive mass spectrometry system, coupled with C18 reverse phase liquid chromatography. Differences in plasma metabolites between adolescents with and without nonalcoholic fatty liver disease (NAFLD) were determined by independent t tests and visualized using Manhattan plots. Untargeted pathway analyses using Mummichog were performed among the significant metabolites to identify pathways that were most dysregulated in NAFLD. Results The metabolomics analysis yielded 9583 metabolites, and 7711 with 80% presence across all samples remained for statistical testing. Of these, 478 metabolites were associated with the presence of NAFLD compared with the matched controls. Pathway analysis revealed that along with lipid metabolism, several major amino acid pathways were dysregulated in NAFLD, with tyrosine metabolism being the most affected. Conclusions Metabolic pathways of several amino acids are significantly disturbed in adolescents with elevated hepatic steatosis. This is a novel finding and suggests that these pathways may be integral in the mechanisms of NAFLD.</description><subject>Adolescent</subject><subject>Amino Acids - metabolism</subject><subject>Case-Control Studies</subject><subject>Child</subject><subject>Female</subject><subject>Humans</subject><subject>Liver - pathology</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Male</subject><subject>Metabolomics - methods</subject><subject>Non-alcoholic Fatty Liver Disease - complications</subject><subject>Non-alcoholic Fatty Liver Disease - metabolism</subject><subject>Obesity - metabolism</subject><subject>Pediatrics</subject><subject>Prospective Studies</subject><issn>0022-3476</issn><issn>1097-6833</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFks9u1DAYxC0EotvCEyAhHzmQ4D9JnBxAigqlSAtIlJ4tr_2l68WJt7ZTtLdeufOEPAletuXAhZNl6TcejWcQekZJSQltXm3KzRZMLFm-lISWhDUP0IKSThRNy_lDtCCEsYJXojlCxzFuCCFdRchjdMSatm5pVy_Qj360k8e9tgZ_hKRW3tk4Yhtx7xIEMNhOuDfeQdQwpYi_27TGn_yknPbrDGt8plLa4aW9gYDf2ggqwq_bn_2EL6ekwhUkMC_xub1a4y8QvZuT9dO9lx-tjvgizWb3BD0alIvw9O48QZdn776enhfLz-8_nPbLQld1lwrdMgW8ZpwaOoAWHVcr3dFBrDjTjIPoKqpEVxtSCyOEqStjKiFYMxhNBXT8BL04vLsN_nqGmORoczbn1AR-jpKKthJVw2mdUX5AdfAxBhjkNthRhZ2kRO47kBv5pwO570ASKnMHWfX8zmBejWD-au4_PQOvDwDkmDcWgozawqTB2AA6SePtfwze_KPXzk5WK_cNdhA3fg65npxERiaJvNjPYL8C2uQFsFbw30QwsEM</recordid><startdate>20160501</startdate><enddate>20160501</enddate><creator>Jin, Ran, PhD</creator><creator>Banton, Sophia, MS, MPH</creator><creator>Tran, ViLinh T., PhD</creator><creator>Konomi, Juna V., PhD</creator><creator>Li, Shuzhao, PhD</creator><creator>Jones, Dean P., PhD</creator><creator>Vos, Miriam B., MD, MSPH</creator><general>Elsevier Inc</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>7X8</scope><orcidid>https://orcid.org/0000-0002-9352-6380</orcidid></search><sort><creationdate>20160501</creationdate><title>Amino Acid Metabolism is Altered in Adolescents with Nonalcoholic Fatty Liver Disease—An Untargeted, High Resolution Metabolomics Study</title><author>Jin, Ran, PhD ; Banton, Sophia, MS, MPH ; Tran, ViLinh T., PhD ; Konomi, Juna V., PhD ; Li, Shuzhao, PhD ; Jones, Dean P., PhD ; Vos, Miriam B., MD, MSPH</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-c82ae35231d1fec793abc91f7b32c23e7941a795d057d77d54dd47726fdc17e93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adolescent</topic><topic>Amino Acids - metabolism</topic><topic>Case-Control Studies</topic><topic>Child</topic><topic>Female</topic><topic>Humans</topic><topic>Liver - pathology</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Male</topic><topic>Metabolomics - methods</topic><topic>Non-alcoholic Fatty Liver Disease - complications</topic><topic>Non-alcoholic Fatty Liver Disease - metabolism</topic><topic>Obesity - metabolism</topic><topic>Pediatrics</topic><topic>Prospective Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jin, Ran, PhD</creatorcontrib><creatorcontrib>Banton, Sophia, MS, MPH</creatorcontrib><creatorcontrib>Tran, ViLinh T., PhD</creatorcontrib><creatorcontrib>Konomi, Juna V., PhD</creatorcontrib><creatorcontrib>Li, Shuzhao, PhD</creatorcontrib><creatorcontrib>Jones, Dean P., PhD</creatorcontrib><creatorcontrib>Vos, Miriam B., MD, MSPH</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of pediatrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jin, Ran, PhD</au><au>Banton, Sophia, MS, MPH</au><au>Tran, ViLinh T., PhD</au><au>Konomi, Juna V., PhD</au><au>Li, Shuzhao, PhD</au><au>Jones, Dean P., PhD</au><au>Vos, Miriam B., MD, MSPH</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amino Acid Metabolism is Altered in Adolescents with Nonalcoholic Fatty Liver Disease—An Untargeted, High Resolution Metabolomics Study</atitle><jtitle>The Journal of pediatrics</jtitle><addtitle>J Pediatr</addtitle><date>2016-05-01</date><risdate>2016</risdate><volume>172</volume><spage>14</spage><epage>19.e5</epage><pages>14-19.e5</pages><issn>0022-3476</issn><eissn>1097-6833</eissn><abstract>Objective To conduct an untargeted, high resolution exploration of metabolic pathways that was altered in association with hepatic steatosis in adolescents. Study design This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17 years evaluated for hepatic steatosis using magnetic resonance spectroscopy. Of these 39 individuals, 30 had hepatic steatosis ≥5% and 9 were matched controls with hepatic steatosis <5%. Fasting plasma samples were analyzed in triplicate using ultra-high resolution metabolomics on a Thermo Fisher Q Exactive mass spectrometry system, coupled with C18 reverse phase liquid chromatography. Differences in plasma metabolites between adolescents with and without nonalcoholic fatty liver disease (NAFLD) were determined by independent t tests and visualized using Manhattan plots. Untargeted pathway analyses using Mummichog were performed among the significant metabolites to identify pathways that were most dysregulated in NAFLD. Results The metabolomics analysis yielded 9583 metabolites, and 7711 with 80% presence across all samples remained for statistical testing. Of these, 478 metabolites were associated with the presence of NAFLD compared with the matched controls. Pathway analysis revealed that along with lipid metabolism, several major amino acid pathways were dysregulated in NAFLD, with tyrosine metabolism being the most affected. Conclusions Metabolic pathways of several amino acids are significantly disturbed in adolescents with elevated hepatic steatosis. This is a novel finding and suggests that these pathways may be integral in the mechanisms of NAFLD.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26858195</pmid><doi>10.1016/j.jpeds.2016.01.026</doi><orcidid>https://orcid.org/0000-0002-9352-6380</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Amino Acids - metabolism Case-Control Studies Child Female Humans Liver - pathology Magnetic Resonance Spectroscopy Male Metabolomics - methods Non-alcoholic Fatty Liver Disease - complications Non-alcoholic Fatty Liver Disease - metabolism Obesity - metabolism Pediatrics Prospective Studies |
| title | Amino Acid Metabolism is Altered in Adolescents with Nonalcoholic Fatty Liver Disease—An Untargeted, High Resolution Metabolomics Study |
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