title: Identification of Potential Plasma Biomarkers for Nonalcoholic Fatty Liver Disease by Integrating Transcriptomics and Proteomics in Laying Hens.
abstract: Background:Prevalent worldwide obesity is associated with increased incidence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. The identification of noninvasive biomarkers for NAFLD is of recent interest. Because primary de novo lipogenesis occurs in chicken liver as in human liver, adult chickens with age-associated steatosis resembling human NAFLD is an appealing animal model.Objective:The objective of this study was to screen potential biomarkers in the chicken model for NAFLD by transcriptomic and proteomic analysis.Methods:Hy-Line W-36 laying hens were fed standard feed from 25 to 45 wk of age to induce fatty liver. They were killed every 4 wk, and liver and plasma were collected at each time point to assess fatty liver development and for transcriptomic and proteomic analysis. Next, selected biomarkers were confirmed in additional experiments by providing supplements of the hepatoprotective nutrients betaine [300, 600, or 900 parts per million (ppm) in vivo; 2 mM in vitro] or docosahexaenoic acid (DHA; 1% in vivo; 100 μM in vitro) to 30-wk-old Hy-Line W-36 laying hens for 4 mo and to Hy-Line W-36 chicken primary hepatocytes with oleic acid-induced steatosis. Liver or hepatocyte lipid contents and the expression of biomarkers were then examined.Results:Plasma acetoacetyl-CoA synthetase (AACS), dipeptidyl-peptidase 4 (DPP4), glutamine synthetase (GLUL), and glutathioneS-transferase (GST) concentrations are well-established biomarkers for NAFLD. Selected biomarkers had significant positive associations with hepatic lipid deposition (P< 0.001). Betaine (900 ppm in vivo; 2 mM in vitro) and DHA (1% in vivo; 100 μM in vitro) supplementation both resulted in lower steatosis accompanied by the reduced expression of selected biomarkers in vivo and in vitro (P< 0.05).Conclusion:This study used adult laying hens to identify biomarkers for NAFLD and indicated that AACS, DPP4, GLUL, and GST could be considered to be potential diagnostic indicators for NAFLD in the future.
authors.affiliation: Department of Animal Science and Technology and.
authors.forename: Meng-Tsz
authors.initials: MT
authors.lastname: Tsai
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei City, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Animal Science and Technology and.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei City, Taiwan.
authors.forename: Mong-Hsun
authors.initials: MH
authors.lastname: Tsai
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei City, Taiwan; and.|Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei City, Taiwan.
authors.forename: Chia-Li
authors.initials: CL
authors.lastname: Han
authors.affiliation: Institute of Chemistry, Academia Sinica, Taipei City, Taiwan; and.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Animal Science and Technology and.
authors.forename: Harry J
authors.initials: HJ
authors.lastname: Mersmann
authors.affiliation: Department of Animal Science and Technology and sding@ntu.edu.tw.|Institute of Biotechnology, National Taiwan University, Taipei City, Taiwan.
authors.forename: Shih-Torng
authors.identifier: 0000-0002-9866-1776
authors.initials: ST
authors.lastname: Ding
mesh_terms: D000818:Animals; D001622:Betaine / Q000097:blood; D015415:Biomarkers; D001715:Bird Diseases / Q000097:blood* / Q000175:diagnosis; D002645:Chickens / Q000097:blood*; D004281:Docosahexaenoic Acids / Q000097:blood; D005234:Fatty Liver / Q000097:blood / Q000175:diagnosis / Q000662:veterinary*; D005260:Female; D040901:Proteomics / Q000379:methods*; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D004281:Docosahexaenoic Acids; D001622:Betaine
keywords: betaine; docosahexaenoic acid; nonalcoholic fatty liver disease; proteomics; transcriptomics