
Alexander Perfilyev
Assistant researcher

Serum aromatic and branched-chain amino acids associated with NASH demonstrate divergent associations with serum lipids
Author
Summary, in English
Background & Aims: Non-alcoholic fatty liver disease (NAFLD) has been associated with multiple metabolic abnormalities. By applying a non-targeted metabolomics approach, we aimed at investigating whether serum metabolite profile that associates with NAFLD would differ in its association with NAFLD-related metabolic risk factors. Methods & Results: A total of 233 subjects (mean ± SD: 48.3 ± 9.3 years old; BMI: 43.1 ± 5.4 kg/m2; 64 male) undergoing bariatric surgery were studied. Of these participants, 164 with liver histology could be classified as normal liver (n = 79), simple steatosis (SS, n = 40) or non-alcoholic steatohepatitis (NASH, n = 45). Among the identified fasting serum metabolites with higher levels in those with NASH when compared to those with normal phenotype were the aromatic amino acids (AAAs: tryptophan, tyrosine and phenylalanine), the branched-chain amino acids (BCAAs: leucine and isoleucine), a phosphatidylcholine (PC(16:0/16:1)) and uridine (all FDRp < 0.05). Only tryptophan was significantly higher in those with NASH compared to those with SS (FDRp < 0.05). Only the AAAs tryptophan and tyrosine correlated positively with serum total and LDL cholesterol (FDRp < 0.1), and accordingly, with liver LDLR at mRNA expression level. In addition, tryptophan was the single AA associated with liver DNA methylation of CpG sites known to be differentially methylated in those with NASH. Conclusions: We found that serum levels of the NASH-related AAAs and BCAAs demonstrate divergent associations with serum lipids. The specific correlation of tryptophan with LDL-c may result from the molecular events affecting LDLR mRNA expression and NASH-associated methylation of genes in the liver.
Department/s
- Diabetes - Epigenetics
- EXODIAB: Excellence of Diabetes Research in Sweden
Publishing year
2021
Language
English
Pages
754-763
Publication/Series
Liver International
Volume
41
Issue
4
Document type
Journal article
Publisher
Wiley-Blackwell
Topic
- Endocrinology and Diabetes
Keywords
- aromatic amino acids
- DNA methylation
- epigenetics
- LDL cholesterol
- NAFLD
- NASH
- non-targeted metabolomics
- tryptophan
Status
Published
Research group
- Diabetes - Epigenetics
ISBN/ISSN/Other
- ISSN: 1478-3223