Lower adropin expression is associated with oxidative stress and severity of nonalcoholic fatty liver disease

Free Radic Biol Med. 2020 Nov 20;160:191-198. doi: 10.1016/j.freeradbiomed.2020.08.005. Epub 2020 Aug 15.

Abstract

Background & aims: Adropin has been reported to be involved in metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). However, the clinical relevance of adropin expression to the histological severity of NAFLD is unclear. This study aimed to investigate adropin expression in biopsy-proven NAFLD patients.

Methods: This case-control study enrolled a total of 109 participants, including 15 normal histological controls, 26 nonalcoholic fatty liver (NAFL), 21 nonalcoholic steatohepatitis (NASH) subjects and B-ultrasound NAFLD-free normal controls matched to the cases based on age and sex (the case:control ratio was 1:1). Liver biopsies were obtained and histological characteristics were assessed. Primary murine hepatocytes were isolated from C57BL/6J mice and incubated with doses of palmitate to induce oxidative stress.

Results: The serum adropin level in NASH patients was 9.99 ± 5.51 ng/ml, significantly lower than that in B-ultrasound normal controls (22.70 ± 6.32 ng/ml), histological normal controls (21.93 ± 6.63 ng/ml) and NAFL patients (17.82 ± 6.90 ng/ml). Serum adropin levels were negatively correlated with the histological severity of NAFLD. The lower serum adropin level predicted NASH (area under the ROC curve: 87.1%). Adropin expression in serum and liver was also negatively associated with hepatic MDA and serum 8-iso-PGF2α levels. Furthermore, palmitate rather than oleate induced oxidative stress in a dose-dependent manner with a gradient decrease in adropin expression in primary murine hepatocytes. Adropin overexpression or treatment ameliorated palmitate-induced oxidative stress in hepatocytes.

Conclusions: Circulating adropin was inversely associated with the oxidative stress and histological severity of NAFLD. It may play an important role in the development of NAFLD.

Keywords: Adropin; Biomarker; Histology; NASH; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Case-Control Studies
  • Humans
  • Intercellular Signaling Peptides and Proteins* / metabolism
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease* / metabolism
  • Oxidative Stress*

Substances

  • Biomarkers
  • Enho protein, human
  • Enho protein, mouse
  • Intercellular Signaling Peptides and Proteins