University of Oulu

Kaikkonen, J. E., Würtz, P., Suomela, E., Lehtovirta, M., Kangas, A. J., Jula, A., Mikkilä, V., Viikari, J. S.A., Juonala, M., Rönnemaa, T., Hutri-Kähönen, N., Kähönen, M., Lehtimäki, T., Soininen, P., Ala-Korpela, M. and Raitakari, O. T. (2017), Metabolic profiling of fatty liver in young and middle-aged adults: Cross-sectional and prospective analyses of the Young Finns Study. Hepatology, 65: 491–500. doi:10.1002/hep.28899

Metabolic profiling of fatty liver in young and middle-aged adults : cross-sectional and prospective analyses of the young Finns study

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Author: Kaikkonen, Jari E.1,2; Würtz, Peter3; Suomela, Emmi1;
Organizations: 1Research Centre of Applied and Preventive Cardiovascular Medicine University of Turku Turku Finland
2Department of Clinical Physiology and Nuclear Medicine Kuopio University Hospital and University of Eastern Finland Kuopio Finland
3Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
4National Institute for Health and Welfare, Turku, Finland
5Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
6Division of Nutrition, Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland
7Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland
8Department of Pediatrics and Department of Clinical Physiology, Tampere University Hospital and University of Tampere, Tampere, Finland
9Department of Clinical Physiology, Tampere University Hospital and University of Tampere, Tampere, Finland
10Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland
11NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
12School of Social and Community Medicine and Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom
13Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
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Language: English
Published: John Wiley & Sons, 2017
Publish Date: 2017-03-24


Nonalcoholic fatty liver is associated with obesity-related 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-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based 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 34–49 years (19% prevalence). Cross-sectional associations as well as 4-year and 10-year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P < 0.0007 for 60 measures in age-adjusted and sex-adjusted cross-sectional analyses). The strongest direct associations were observed for extremely large very-low-density lipoprotein triglycerides (odds ratio [OR] 5 4.86 per 1 standard deviation, 95% confidence interval 3.48–6.78), other very-low-density lipoprotein measures, and branched-chain amino acids (e.g., leucine OR = 2.94, 2.51–3.44). Strong inverse associations were observed for high-density lipoprotein measures, e.g., high-density lipoprotein size (OR = 0.36, 0.30–0.42) and several fatty acids including omega-6 (OR = 0.37, 0.32–0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P < 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis.

Conclusion: 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.

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Series: Hepatology
ISSN: 0270-9139
ISSN-E: 1527-3350
ISSN-L: 0270-9139
Volume: 65
Issue: 2
Pages: 491 - 500
DOI: 10.1002/hep.28899
Type of Publication: A1 Journal article – refereed
Field of Science: 3142 Public health care science, environmental and occupational health
Funding: Supported by the Academy of Finland (134309, 126925, 121584, 124282, 129378, 117797, 141071, 286284); the Social Insurance Institution of Finland; Kuopio, Tampere, and Turku University Hospital Medical Funds; Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation of Cardiovascular Research; Finnish Cultural Foundation; Emil Aaltonen Foundation; and Yrjö Jahnsson Foundation. The serum NMR metabolomics platform and its development have been supported by Strategic Research Funding from the University of Oulu, the Academy of Finland (294834), the Novo Nordisk Foundation, the Sigrid Juselius Foundation, the Yrjö Jahnsson Foundation, and the Finnish Diabetes Research Foundation.
Academy of Finland Grant Number: 134309
Detailed Information: 134309 (Academy of Finland Funding decision)
126925 (Academy of Finland Funding decision)
121584 (Academy of Finland Funding decision)
124282 (Academy of Finland Funding decision)
129378 (Academy of Finland Funding decision)
117797 (Academy of Finland Funding decision)
141071 (Academy of Finland Funding decision)
286284 (Academy of Finland Funding decision)
294834 (Academy of Finland Funding decision)
Copyright information: Copyright © 2016 The Authors. HEPATOLOGY published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.