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Discovery of dipeptidyl peptidase-4 inhibitor specific biomarker in non-alcoholic fatty liver disease mouse models using modified basket trial
- Title
- Discovery of dipeptidyl peptidase-4 inhibitor specific biomarker in non-alcoholic fatty liver disease mouse models using modified basket trial
- Authors
- Oh, Ju Hee; Jun, Dae Won; Kim, Hye Young; Lee, Seung Min; Yoon, Eileen L.; Hwang, Jungwook; Park, Jung Hwan; Lee, Hanbi; Kim, Wankyu; Kim, Hyunsung
- Ewha Authors
- 김완규
- SCOPUS Author ID
- 김완규
- Issue Date
- 2022
- Journal Title
- CLINICAL AND MOLECULAR HEPATOLOGY
- ISSN
- 2287-2728
2287-285X
- Citation
- CLINICAL AND MOLECULAR HEPATOLOGY vol. 28, no. 3, pp. 497 - 509
- Keywords
- Biopsy; Nonalcoholic fatty liver disease; Dipeptidyl peptidase 4 inhibitor; Insulin-like growth factor binding protein 1; Biomarker
- Publisher
- KOREAN ASSOC STUDY LIVER
- Indexed
- SCIE; SCOPUS; KCI
- Document Type
- Article
- Abstract
- Background/Aims: We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD). Methods: An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy. Results: DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels. Conclusions: The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.
- DOI
- 10.3350/cmh.2022.0019
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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