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  • de Mello, Vanessa D.University of Eastern Finland (author)

Serum aromatic and branched-chain amino acids associated with NASH demonstrate divergent associations with serum lipids

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2020-12-05
  • Wiley,2021

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  • LIBRIS-ID:oai:lup.lub.lu.se:eebf59c1-4526-4298-81e3-e07e1379f749
  • https://lup.lub.lu.se/record/eebf59c1-4526-4298-81e3-e07e1379f749URI
  • https://doi.org/10.1111/liv.14743DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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  • 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.

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  • Sehgal, RatikaUniversity of Eastern Finland (author)
  • Männistö, VilleUniversity of Eastern Finland (author)
  • Klåvus, AntonUniversity of Eastern Finland (author)
  • Nilsson, Emma ALund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups(Swepub:lu)endo-eca (author)
  • Perfilyev, AlexanderLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups(Swepub:lu)med-apy (author)
  • Kaminska, DorotaUniversity of Eastern Finland (author)
  • Miao, ZongUniversity of California, Los Angeles (author)
  • Pajukanta, PäiviUniversity of California, Los Angeles (author)
  • Ling, CharlotteLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups(Swepub:lu)endo-cl0 (author)
  • Hanhineva, KatiUniversity of Eastern Finland,University of Turku (author)
  • Pihlajamäki, JussiUniversity of Eastern Finland,Kuopio University Hospital (author)
  • University of Eastern FinlandDiabetes - epigenetik (creator_code:org_t)

Related titles

  • In:Liver International: Wiley41:4, s. 754-7631478-32231478-3231

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