Hepatic transcriptome signature correlated with HOMA-IR explains early nonalcoholic fatty liver disease pathogenesis
Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) is multistage with heterogeneous outcomes. We studied the influence of insulin resistance (IR) on the hepatic transcriptome of early NAFLD stages, to understand disease development. Materials and methods: In this cross-sectional...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Annals of Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268120300703 |
| _version_ | 1818837381418057728 |
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| author | Ankita Chatterjee Analabha Basu Kausik Das Pankaj Singh Dipankar Mondal Biswanath Bhattacharya Shweta Roychoudhury Partha P. Majumder Abhijit Chowdhury Priyadarshi Basu |
| author_facet | Ankita Chatterjee Analabha Basu Kausik Das Pankaj Singh Dipankar Mondal Biswanath Bhattacharya Shweta Roychoudhury Partha P. Majumder Abhijit Chowdhury Priyadarshi Basu |
| author_sort | Ankita Chatterjee |
| collection | DOAJ |
| description | Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) is multistage with heterogeneous outcomes. We studied the influence of insulin resistance (IR) on the hepatic transcriptome of early NAFLD stages, to understand disease development. Materials and methods: In this cross-sectional study, possible clinicopathological risk factors were compared between mild-NAFL (N = 72) and non-alcoholic steatohepatitis (NASH; N = 51) patients. Liver tissue-transcriptome difference was studied between a subset of 25 mild-NAFL and 20 NASH biopsies and validated on another subset of 12 mild-NAFL and 13 NASH biopsies, using RT-PCR. The relationship between IR driven gene expression changes with fibrosis in NASH was investigated. Results: Significantly higher weight (p = 0.005) and elevated levels of HbA1c (p = 0.009), FBG (p = 0.03) and HOMA-IR (p = 0.009) were found in NASH patients. Five differentially expressed genes (DEGs, fold change > 1.5) were identified in NASH-FABP4, FABP5L2, CD24, PRAP1, and SPP1. The DEGs were positively associated with disease severity and HOMA-IR, and were found to be efficient classifiers of mild-NAFL and NASH. Additional 1218 genes identified related to IR (IrCGs), which can classify NASH-with-fibrosis patients separately from mild-NAFL and NASH patients. IrCGs can promote intra-hepatic fat accumulation, dysregulation of the lipid metabolism, lipotoxicity, and activation of cell survival pathways including activation of cell proliferation and differentiation pathways. Conclusions: Hepatic expression of genes associated with insulin resistance may drive NAFLD development and progression. |
| first_indexed | 2024-12-19T03:21:36Z |
| format | Article |
| id | doaj.art-57b57b177f66460ea041a797552cc702 |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-12-19T03:21:36Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-57b57b177f66460ea041a797552cc7022022-12-21T20:37:45ZengElsevierAnnals of Hepatology1665-26812020-09-01195472481Hepatic transcriptome signature correlated with HOMA-IR explains early nonalcoholic fatty liver disease pathogenesisAnkita Chatterjee0Analabha Basu1Kausik Das2Pankaj Singh3Dipankar Mondal4Biswanath Bhattacharya5Shweta Roychoudhury6Partha P. Majumder7Abhijit Chowdhury8Priyadarshi Basu9National Institute of Biomedical Genomics, Kalyani, West Bengal, IndiaNational Institute of Biomedical Genomics, Kalyani, West Bengal, IndiaInstitute of Post Graduate Medical Education and Research, Kolkata, West Bengal, IndiaInstitute of Post Graduate Medical Education and Research, Kolkata, West Bengal, IndiaInstitute of Post Graduate Medical Education and Research, Kolkata, West Bengal, IndiaNational Institute of Biomedical Genomics, Kalyani, West Bengal, IndiaNational Institute of Biomedical Genomics, Kalyani, West Bengal, IndiaNational Institute of Biomedical Genomics, Kalyani, West Bengal, IndiaInstitute of Post Graduate Medical Education and Research, Kolkata, West Bengal, IndiaNational Institute of Biomedical Genomics, Kalyani, West Bengal, India; Corresponding author.Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) is multistage with heterogeneous outcomes. We studied the influence of insulin resistance (IR) on the hepatic transcriptome of early NAFLD stages, to understand disease development. Materials and methods: In this cross-sectional study, possible clinicopathological risk factors were compared between mild-NAFL (N = 72) and non-alcoholic steatohepatitis (NASH; N = 51) patients. Liver tissue-transcriptome difference was studied between a subset of 25 mild-NAFL and 20 NASH biopsies and validated on another subset of 12 mild-NAFL and 13 NASH biopsies, using RT-PCR. The relationship between IR driven gene expression changes with fibrosis in NASH was investigated. Results: Significantly higher weight (p = 0.005) and elevated levels of HbA1c (p = 0.009), FBG (p = 0.03) and HOMA-IR (p = 0.009) were found in NASH patients. Five differentially expressed genes (DEGs, fold change > 1.5) were identified in NASH-FABP4, FABP5L2, CD24, PRAP1, and SPP1. The DEGs were positively associated with disease severity and HOMA-IR, and were found to be efficient classifiers of mild-NAFL and NASH. Additional 1218 genes identified related to IR (IrCGs), which can classify NASH-with-fibrosis patients separately from mild-NAFL and NASH patients. IrCGs can promote intra-hepatic fat accumulation, dysregulation of the lipid metabolism, lipotoxicity, and activation of cell survival pathways including activation of cell proliferation and differentiation pathways. Conclusions: Hepatic expression of genes associated with insulin resistance may drive NAFLD development and progression.http://www.sciencedirect.com/science/article/pii/S1665268120300703TranscriptomeNASHInsulin-resistanceFibrosisHOMA-IR |
| spellingShingle | Ankita Chatterjee Analabha Basu Kausik Das Pankaj Singh Dipankar Mondal Biswanath Bhattacharya Shweta Roychoudhury Partha P. Majumder Abhijit Chowdhury Priyadarshi Basu Hepatic transcriptome signature correlated with HOMA-IR explains early nonalcoholic fatty liver disease pathogenesis Annals of Hepatology Transcriptome NASH Insulin-resistance Fibrosis HOMA-IR |
| title | Hepatic transcriptome signature correlated with HOMA-IR explains early nonalcoholic fatty liver disease pathogenesis |
| title_full | Hepatic transcriptome signature correlated with HOMA-IR explains early nonalcoholic fatty liver disease pathogenesis |
| title_fullStr | Hepatic transcriptome signature correlated with HOMA-IR explains early nonalcoholic fatty liver disease pathogenesis |
| title_full_unstemmed | Hepatic transcriptome signature correlated with HOMA-IR explains early nonalcoholic fatty liver disease pathogenesis |
| title_short | Hepatic transcriptome signature correlated with HOMA-IR explains early nonalcoholic fatty liver disease pathogenesis |
| title_sort | hepatic transcriptome signature correlated with homa ir explains early nonalcoholic fatty liver disease pathogenesis |
| topic | Transcriptome NASH Insulin-resistance Fibrosis HOMA-IR |
| url | http://www.sciencedirect.com/science/article/pii/S1665268120300703 |
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