{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T13:53:30Z","timestamp":1793022810282,"version":"4.5.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2016,12,24]],"date-time":"2016-12-24T00:00:00Z","timestamp":1482537600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>Nonalcoholic fatty liver is associated with obesity\u2010related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis\u2010related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty\u2010eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population\u2010based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34\u201049 years (19% prevalence). Cross\u2010sectional associations as well as 4\u2010year and 10\u2010year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.0007 for 60 measures in age\u2010adjusted and sex\u2010adjusted cross\u2010sectional analyses). The strongest direct associations were observed for extremely large very\u2010low\u2010density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48\u20106.78), other very\u2010low\u2010density lipoprotein measures, and branched\u2010chain amino acids (e.g., leucine OR = 2.94, 2.51\u20103.44). Strong inverse associations were observed for high\u2010density lipoprotein measures, e.g., high\u2010density lipoprotein size (OR = 0.36, 0.30\u20100.42) and several fatty acids including omega\u20106 (OR = 0.37, 0.32\u20100.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (H<jats:sc>epatology<\/jats:sc> 2017;65:491\u2010500).<\/jats:p>","DOI":"10.1002\/hep.28899","type":"journal-article","created":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T14:52:42Z","timestamp":1477320762000},"page":"491-500","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":117,"title":["Metabolic profiling of fatty liver in young and middle\u2010aged adults: Cross\u2010sectional and prospective analyses of the Young Finns Study"],"prefix":"10.1097","volume":"65","author":[{"given":"Jari E.","family":"Kaikkonen","sequence":"first","affiliation":[{"name":"Research Centre of Applied and Preventive Cardiovascular Medicine,University of Turku,Turku,Finland"},{"name":"Department of Clinical Physiology and Nuclear Medicine,Kuopio University Hospital and University of Eastern Finland,Kuopio,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"W\u00fcrtz","sequence":"additional","affiliation":[{"name":"Computational Medicine, Faculty of Medicine,University of Oulu and Biocenter Oulu,Oulu,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmi","family":"Suomela","sequence":"additional","affiliation":[{"name":"Research Centre of Applied and Preventive Cardiovascular Medicine,University of Turku,Turku,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miia","family":"Lehtovirta","sequence":"additional","affiliation":[{"name":"Research Centre of Applied and Preventive Cardiovascular Medicine,University of Turku,Turku,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti J.","family":"Kangas","sequence":"additional","affiliation":[{"name":"Computational Medicine, Faculty of Medicine,University of Oulu and Biocenter Oulu,Oulu,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antti","family":"Jula","sequence":"additional","affiliation":[{"name":"National Institute for Health and Welfare,Turku,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Mikkil\u00e4","sequence":"additional","affiliation":[{"name":"Research Centre of Applied and Preventive Cardiovascular Medicine,University of Turku,Turku,Finland"},{"name":"Division of Nutrition, Department of Food and Environmental Sciences,University of Helsinki,Helsinki,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorma S.A.","family":"Viikari","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Turku and Division of Medicine, Turku University Hospital,Turku,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Juonala","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Turku and Division of Medicine, Turku University Hospital,Turku,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tapani","family":"R\u00f6nnemaa","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Turku and Division of Medicine, Turku University Hospital,Turku,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Hutri\u2010K\u00e4h\u00f6nen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Tampere University Hospital and University of Tampere,Tampere,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"K\u00e4h\u00f6nen","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology,Tampere University Hospital and University of Tampere,Tampere,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terho","family":"Lehtim\u00e4ki","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine,University of Tampere,Tampere,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasi","family":"Soininen","sequence":"additional","affiliation":[{"name":"Computational Medicine, Faculty of Medicine,University of Oulu and Biocenter Oulu,Oulu,Finland"},{"name":"NMR Metabolomics Laboratory, School of Pharmacy,University of Eastern Finland,Kuopio,Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Ala\u2010Korpela","sequence":"additional","affiliation":[{"name":"Computational Medicine, Faculty of Medicine,University of Oulu and Biocenter Oulu,Oulu,Finland"},{"name":"NMR Metabolomics Laboratory, School of Pharmacy,University of Eastern Finland,Kuopio,Finland"},{"name":"School of Social and Community Medicine,University of Bristol,Bristol,United Kingdom"},{"name":"Medical Research Council Integrative Epidemiology Unit,University of Bristol,Bristol,United 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