A1 Journal article – refereed
Metabolic profiling of fatty liver in young and middle-aged adults: Cross-sectional and prospective analyses of the Young Finns Study




List of Authors: Kaikkonen JE, Würtz P, Suomela E, Lehtovirta M, Kangas AJ, Jula A, Mikkilä V, Viikari JS, Juonala M, Rönnemaa T, Hutri-Kähönen N, Kähönen M, Lehtimäki T, Soininen P, Ala-Korpela M, Raitakari OT
Publisher: Wiley
Publication year: 2017
Journal: Hepatology
Volume number: 65
Issue number: 2
Number of pages: 10

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.


Last updated on 2019-20-07 at 18:02