Identified in blood diet-related methylation changes stratify liver biopsies of NAFLD patients according to fibrosis grade

Clinical Epigenetics

Research

Dominik Strapagiel¹  Justyna Jarczak²  Karolina Skonieczna-Żydecka³  Joanna Palma³  Marcin Ufnal⁴  Bogusław Machaliński⁵  Magdalena Baśkiewicz-Hałasa⁵  Ewa Stachowska⁶  Viktoria Hawryłkowicz⁶  Dominika Maciejewska-Markiewicz⁶  Patrycja Załęcka⁶  Karina Ryterska⁶  Tomasz Kazimierz Wojdacz⁷  Jan Bińkowski⁷  Katarzyna Ewa Sokolowska⁷  Konrad Borowski⁷  Olga Taryma-Leśniak⁷  Katarzyna Kozlowska-Petriczko⁸ 

[1] Biobank Laboratory, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237, Lodz, Poland;Biobank Laboratory, Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-237, Lodz, Poland;Laboratory of Molecular Basis of Behavior, Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland;Department of Biochemical Sciences, Pomeranian Medical University, 71-460, Szczecin, Poland;Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 02-097, Warsaw, Poland;Department of General Pathology, Pomeranian Medical University, 70-111, Szczecin, Poland;Department of Human Nutrition and Metabolomics, Pomeranian Medical University, 71-460, Szczecin, Poland;Independent Clinical Epigenetics Laboratory, Pomeranian Medical University, Unii Lubelskiej 1, 71-252, Szczecin, Poland;Translational Medicine Group, Pomeranian Medical University, 70-204, Szczecin, Poland;Department of Gastroenterology and Internal Medicine, SPWSZ Hospital, 71-455, Szczecin, Poland;

关键词: Nutrition;    Non-alcoholic fatty liver disease;    Liver;    Fibre;    DNA methylation;    Epigenetics;    Acetylation;    Mediterranean diet;   

DOI  :  10.1186/s13148-022-01377-6

 received in 2022-04-12, accepted in 2022-11-15,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundHigh caloric diet and lack of physical activity are considered main causes of NAFLD, and a change in the diet is still the only effective treatment of this disease. However, molecular mechanism of the effectiveness of diet change in treatment of NAFLD is poorly understood. We aimed to assess the involvement of epigenetic mechanisms of gene expression regulation in treatment of NAFLD. Eighteen participants with medium- to high-grade steatosis were recruited and trained to follow the Mediterranean diet modified to include fibre supplements. At three timepoints (baseline, after 30 and 60 days), we evaluated adherence to the diet and measured a number of physiological parameters such as anthropometry, blood and stool biochemistry, liver steatosis and stiffness. We also collected whole blood samples for genome-wide methylation profiling and histone acetylation assessment.ResultsThe diet change resulted in a decrease in liver steatosis along with statistically significant, but a minor change in BMI and weight of our study participants. The epigenetic profiling of blood cells identified significant genome-wide changes of methylation and acetylation with the former not involving regions directly regulating gene expression. Most importantly, we were able to show that identified blood methylation changes occur also in liver cells of NAFLD patients and the machine learning-based classifier that we build on those methylation changes was able to predict the stage of liver fibrosis with ROC AUC = 0.9834.ConclusionMethylomes of blood cells from NAFLD patients display a number of changes that are most likely a consequence of unhealthy diet, and the diet change appears to reverse those epigenetic changes. Moreover, the methylation status at CpG sites undergoing diet-related methylation change in blood cells stratifies liver biopsies from NAFLD patients according to fibrosis grade.

【 授权许可】

CC BY   
© The Author(s) 2022

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