{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:21:53Z","timestamp":1793362913456,"version":"4.5.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK111038"],"award-info":[{"award-number":["R01DK111038"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK114504"],"award-info":[{"award-number":["R01DK114504"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nutr. Diabetes"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>Growth differentiation factor 15 (GDF15) has been associated with food intake and weight regulation in response to metabolic stress. In animal models, it has been noted that it may play a role in the progression of non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver disease in children.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Design<\/jats:title>\n                <jats:p>In the current study, we explored the association of circulating plasma concentrations of GDF15 with NAFLD in youth with overweight\/obesity, and whether changes in plasma concentrations in GDF15 parallel the changes in intrahepatic fat content (HFF%) over time.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Plasma GDF15 concentrations were measured by ELISA in 175 youth with overweight\/obesity who underwent an oral glucose tolerance test (OGTT) and magnetic resonance imaging (MRI) to assess intrahepatic, visceral, and subcutaneous fat. Baseline fasting GDF15 concentrations were measured in twenty-two overweight\/obese youth who progressed (<jats:italic>n<\/jats:italic>\u2009=\u200911) or regressed (<jats:italic>n<\/jats:italic>\u2009=\u200911) in HFF% by more than 30% of original over a 2-year period.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Youth with NAFLD had significantly higher plasma concentrations of GDF15 than those without NAFLD, independent of age, sex, ethnicity, BMI <jats:italic>z<\/jats:italic>-score (BMIz), and visceral fat (<jats:italic>P<\/jats:italic>\u2009=\u20090.002). During the OGTT, there was a decline in plasma GDF15 concentrations from 0 to 60\u2009min, but GDF15 concentrations returned to basal levels by the end of the study. There was a statistically significant association between change in HFF% and change in GDF15 (<jats:italic>P<\/jats:italic>\u2009=\u20090.008; <jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090.288) over ~2 years of follow-up.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These data suggest that plasma GDF15 concentrations change with change in intrahepatic fat content in youth with overweight\/obesity and may serve as a biomarker for NAFLD in children.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1038\/s41387-022-00187-2","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T18:03:05Z","timestamp":1645552985000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Growth differentiation factor 15 (GDF15) is associated with non-alcoholic fatty liver disease (NAFLD) in youth with overweight or obesity"],"prefix":"10.1038","volume":"12","author":[{"given":"Brittany","family":"Galuppo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7898-8990","authenticated-orcid":false,"given":"Cristiana","family":"Agazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Pierpont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Chick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Caprio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-4173","authenticated-orcid":false,"given":"Nicola","family":"Santoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"187_CR1","doi-asserted-by":"publisher","first-page":"e0140908","DOI":"10.1371\/journal.pone.0140908","volume":"10","author":"EL Anderson","year":"2015","unstructured":"Anderson EL, Howe LD, Jones HE, Higgins JP, Lawlor DA, Fraser A. The prevalence of non-alcoholic fatty liver disease in children and adolescents: a systematic review and meta-analysis. PLoS ONE. 2015;10:e0140908.","journal-title":"PLoS ONE"},{"key":"187_CR2","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1002\/hep.30035","volume":"68","author":"D Trico","year":"2018","unstructured":"Trico D, Caprio S, Rosaria Umano G, Pierpont B, Nouws J, Galderisi A, et al. Metabolic features of nonalcoholic fatty liver (NAFL) in obese adolescents: findings from a multiethnic cohort. Hepatology. 2018;68:1376\u201390.","journal-title":"Hepatology"},{"key":"187_CR3","doi-asserted-by":"publisher","first-page":"217","DOI":"10.4254\/wjh.v6.i4.217","volume":"6","author":"P Marzuillo","year":"2014","unstructured":"Marzuillo P, Del Giudice EM, Santoro N. Pediatric non-alcoholic fatty liver disease: new insights and future directions. World J Hepatol. 2014;6:217\u201325.","journal-title":"World J Hepatol"},{"key":"187_CR4","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1016\/j.pcl.2011.07.005","volume":"58","author":"E D\u2019Adamo","year":"2011","unstructured":"D\u2019Adamo E, Santoro N, Caprio S. Metabolic syndrome in pediatrics: old concepts revised, new concepts discussed. Pediatr Clin North Am. 2011;58:1241\u201355. xi.","journal-title":"Pediatr Clin North Am"},{"key":"187_CR5","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1093\/oxfordjournals.jbchem.a021798","volume":"122","author":"M Yokoyama-Kobayashi","year":"1997","unstructured":"Yokoyama-Kobayashi M, Saeki M, Sekine S, Kato S. Human cDNA encoding a novel TGF-beta superfamily protein highly expressed in placenta. J Biochem. 1997;122:622\u20136.","journal-title":"J Biochem"},{"key":"187_CR6","doi-asserted-by":"publisher","first-page":"3742","DOI":"10.1128\/MCB.20.10.3742-3751.2000","volume":"20","author":"EC Hsiao","year":"2000","unstructured":"Hsiao EC, Koniaris LG, Zimmers-Koniaris T, Sebald SM, Huynh TV, Lee SJ. Characterization of growth-differentiation factor 15, a transforming growth factor beta superfamily member induced following liver injury. Mol Cell Biol. 2000;20:3742\u201351.","journal-title":"Mol Cell Biol"},{"key":"187_CR7","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1038\/nm1677","volume":"13","author":"H Johnen","year":"2007","unstructured":"Johnen H, Lin S, Kuffner T, Brown DA, Tsai VW, Bauskin AR, et al. Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1. Nat Med. 2007;13:1333\u201340.","journal-title":"Nat Med"},{"key":"187_CR8","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/s41586-019-1911-y","volume":"578","author":"AP Coll","year":"2020","unstructured":"Coll AP, Chen M, Taskar P, Rimmington D, Patel S, Tadross JA, et al. GDF15 mediates the effects of metformin on body weight and energy balance. Nature. 2020;578:444\u20138.","journal-title":"Nature"},{"key":"187_CR9","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1038\/nm.4393","volume":"23","author":"PJ Emmerson","year":"2017","unstructured":"Emmerson PJ, Wang F, Du Y, Liu Q, Pickard RT, Gonciarz MD, et al. The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL. Nat Med. 2017;23:1215\u20139.","journal-title":"Nat Med"},{"key":"187_CR10","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1161\/CIRCULATIONAHA.114.011204","volume":"130","author":"L Wallentin","year":"2014","unstructured":"Wallentin L, Hijazi Z, Andersson U, Alexander JH, De Caterina R, Hanna M, et al. Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation. 2014;130:1847\u201358.","journal-title":"Circulation"},{"key":"187_CR11","doi-asserted-by":"crossref","unstructured":"Lockhart SM, Saudek V, O\u2019Rahilly S. GDF15: a hormone conveying somatic distress to the brain. Endocr Rev. 2020;41:bnaa007.","DOI":"10.1210\/endrev\/bnaa007"},{"key":"187_CR12","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/liv.13587","volume":"38","author":"BK Koo","year":"2018","unstructured":"Koo BK, Um SH, Seo DS, Joo SK, Bae JM, Park JH, et al. Growth differentiation factor 15 predicts advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease. Liver Int. 2018;38:695\u2013705.","journal-title":"Liver Int"},{"key":"187_CR13","doi-asserted-by":"publisher","first-page":"276","DOI":"10.5009\/gnl16049","volume":"11","author":"ES Lee","year":"2017","unstructured":"Lee ES, Kim SH, Kim HJ, Kim KH, Lee BS, Ku BJ. Growth differentiation factor 15 predicts chronic liver disease severity. Gut Liver. 2017;11:276\u201382.","journal-title":"Gut Liver"},{"key":"187_CR14","first-page":"1","volume":"11","author":"RJ Kuczmarski","year":"2002","unstructured":"Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, et al. 2000 CDC Growth Charts for the United States: methods and development. Vital Health Stat. 2002;11:1\u2013190.","journal-title":"Vital Health Stat"},{"key":"187_CR15","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/ajg.2018.1","volume":"113","author":"GR Umano","year":"2018","unstructured":"Umano GR, Caprio S, Di Sessa A, Chalasani N, Dykas DJ, Pierpont B, et al. The rs626283 variant in the MBOAT7 gene is associated with insulin resistance and fatty liver in caucasian obese youth. Am J Gastroenterol. 2018;113:376\u201383.","journal-title":"Am J Gastroenterol"},{"key":"187_CR16","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/j.cmet.2017.10.017","volume":"26","author":"S O\u2019Rahilly","year":"2017","unstructured":"O\u2019Rahilly S. GDF15-from biomarker to allostatic hormone. Cell Metab. 2017;26:807\u20138.","journal-title":"Cell Metab"},{"key":"187_CR17","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1016\/j.cell.2019.07.033","volume":"178","author":"HH Luan","year":"2019","unstructured":"Luan HH, Wang A, Hilliard BK, Carvalho F, Rosen CE, Ahasic AM. et al. GDF15 Is an inflammation-induced central mediator of tissue tolerance. Cell. 2019;178:1231\u201344. e1211.","journal-title":"Cell"},{"key":"187_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25098-0","volume":"8","author":"KH Kim","year":"2018","unstructured":"Kim KH, Kim SH, Han DH, Jo YS, Lee YH, Lee MS. Growth differentiation factor 15 ameliorates nonalcoholic steatohepatitis and related metabolic disorders in mice. Sci Rep. 2018;8:6789.","journal-title":"Sci Rep"},{"key":"187_CR19","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.redox.2018.01.013","volume":"16","author":"M Zhang","year":"2018","unstructured":"Zhang M, Sun W, Qian J, Tang Y. Fasting exacerbates hepatic growth differentiation factor 15 to promote fatty acid beta-oxidation and ketogenesis via activating XBP1 signaling in liver. Redox Biol. 2018;16:87\u201396.","journal-title":"Redox Biol"},{"key":"187_CR20","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1016\/j.jhep.2019.12.004","volume":"72","author":"Z Zhang","year":"2020","unstructured":"Zhang Z, Xu X, Tian W, Jiang R, Lu Y, Sun Q, et al. ARRB1 inhibits non-alcoholic steatohepatitis progression by promoting GDF15 maturation. J Hepatol. 2020;72:976\u201389.","journal-title":"J Hepatol"}],"container-title":["Nutrition &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41387-022-00187-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41387-022-00187-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41387-022-00187-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T19:26:49Z","timestamp":1669231609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41387-022-00187-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,22]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["187"],"URL":"https:\/\/doi.org\/10.1038\/s41387-022-00187-2","relation":{},"ISSN":["2044-4052"],"issn-type":[{"value":"2044-4052","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,22]]},"assertion":[{"value":"17 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2022","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"9"}}