Identification of Potential Plasma Biomarkers for Nonalcoholic Fatty Liver Disease by Integrating Transcriptomics and Proteomics in Laying Hens

Meng Tsz Tsai, Yu Jen Chen, Ching Yi Chen, Mong Hsun Tsai, Chia Li Han, Yu Ju Chen, Harry J. Mersmann, Shih Torng Ding

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 glutathione S-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.

Original languageEnglish
Pages (from-to)293-303
Number of pages11
JournalThe Journal of nutrition
Volume147
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

Fingerprint

Proteomics
Biomarkers
Chickens
Liver
Dipeptidyl Peptidase 4
Betaine
acetoacetyl-CoA synthetase
Fatty Liver
Glutathione Transferase
Hepatocytes
Lipids
Glutamate-Ammonia Ligase
Lipogenesis
Non-alcoholic Fatty Liver Disease
Docosahexaenoic Acids
Oleic Acid
Animal Models
Obesity
In Vitro Techniques
Food

Keywords

  • betaine
  • docosahexaenoic acid
  • nonalcoholic fatty liver disease
  • proteomics
  • transcriptomics

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Identification of Potential Plasma Biomarkers for Nonalcoholic Fatty Liver Disease by Integrating Transcriptomics and Proteomics in Laying Hens. / Tsai, Meng Tsz; Chen, Yu Jen; Chen, Ching Yi; Tsai, Mong Hsun; Han, Chia Li; Chen, Yu Ju; Mersmann, Harry J.; Ding, Shih Torng.

In: The Journal of nutrition, Vol. 147, No. 3, 01.03.2017, p. 293-303.

Research output: Contribution to journalArticle

Tsai, Meng Tsz ; Chen, Yu Jen ; Chen, Ching Yi ; Tsai, Mong Hsun ; Han, Chia Li ; Chen, Yu Ju ; Mersmann, Harry J. ; Ding, Shih Torng. / Identification of Potential Plasma Biomarkers for Nonalcoholic Fatty Liver Disease by Integrating Transcriptomics and Proteomics in Laying Hens. In: The Journal of nutrition. 2017 ; Vol. 147, No. 3. pp. 293-303.
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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 glutathione S-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.",
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