Format

Send to

Choose Destination
Hepatology. 2017 Feb;65(2):491-500. doi: 10.1002/hep.28899. Epub 2016 Dec 24.

Metabolic profiling of fatty liver in young and middle-aged adults: Cross-sectional and prospective analyses of the Young Finns Study.

Author information

1
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
2
Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.
3
Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland.
4
National Institute for Health and Welfare, Turku, Finland.
5
Division of Nutrition, Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.
6
Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland.
7
Department of Pediatrics, Tampere University Hospital and University of Tampere, Tampere, Finland.
8
Department of Clinical Physiology, Tampere University Hospital and University of Tampere, Tampere, Finland.
9
Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
10
NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
11
School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
12
Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
13
Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.

Abstract

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] = 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. (Hepatology 2017;65:491-500).

PMID:
27775848
PMCID:
PMC5299457
DOI:
10.1002/hep.28899
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center