Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm
Fatty liver disease is an emerging contributor to disease burden worldwide. The past decades of work established the heterogeneous nature of non-alcoholic fatty liver disease (NAFLD) etiology and systemic contributions to the pathogenesis of the disease. This called for the proposal of a redefinitio...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/14762 |
| _version_ | 1797463139112976384 |
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| author | Damien Chua Zun Siong Low Guo Xiang Cheam Aik Seng Ng Nguan Soon Tan |
| author_facet | Damien Chua Zun Siong Low Guo Xiang Cheam Aik Seng Ng Nguan Soon Tan |
| author_sort | Damien Chua |
| collection | DOAJ |
| description | Fatty liver disease is an emerging contributor to disease burden worldwide. The past decades of work established the heterogeneous nature of non-alcoholic fatty liver disease (NAFLD) etiology and systemic contributions to the pathogenesis of the disease. This called for the proposal of a redefinition in 2020 to that of metabolic dysfunction-associated fatty liver disease (MAFLD) to better reflect the current understanding of the disease. To date, several clinical cohort studies comparing NAFLD and MAFLD hint at the relevancy of the new nomenclature in enriching for patients with more severe hepatic injury and extrahepatic comorbidities. However, the underlying systemic pathogenesis is still not fully understood. Preclinical animal models have been imperative in elucidating key biological mechanisms in various contexts, including intrahepatic disease progression, interorgan crosstalk and systemic dysregulation. Furthermore, they are integral in developing novel therapeutics against MAFLD. However, substantial contextual variabilities exist across different models due to the lack of standardization in several aspects. As such, it is crucial to understand the strengths and weaknesses of existing models to better align them to the human condition. In this review, we consolidate the implications arising from the change in nomenclature and summarize MAFLD pathogenesis. Subsequently, we provide an updated evaluation of existing MAFLD preclinical models in alignment with the new definitions and perspectives to improve their translational relevance. |
| first_indexed | 2024-03-09T17:46:25Z |
| format | Article |
| id | doaj.art-56474903bdaf45fbb950b0a45aa2232f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:46:25Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-56474903bdaf45fbb950b0a45aa2232f2023-11-24T11:07:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123231476210.3390/ijms232314762Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD ParadigmDamien Chua0Zun Siong Low1Guo Xiang Cheam2Aik Seng Ng3Nguan Soon Tan4Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, SingaporeLee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, SingaporeSchool of Biological Sciences, Nanyang Technological University Singapore, 60 Nanyang Drive, Singapore 637551, SingaporeRadcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UKLee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road, Singapore 308232, SingaporeFatty liver disease is an emerging contributor to disease burden worldwide. The past decades of work established the heterogeneous nature of non-alcoholic fatty liver disease (NAFLD) etiology and systemic contributions to the pathogenesis of the disease. This called for the proposal of a redefinition in 2020 to that of metabolic dysfunction-associated fatty liver disease (MAFLD) to better reflect the current understanding of the disease. To date, several clinical cohort studies comparing NAFLD and MAFLD hint at the relevancy of the new nomenclature in enriching for patients with more severe hepatic injury and extrahepatic comorbidities. However, the underlying systemic pathogenesis is still not fully understood. Preclinical animal models have been imperative in elucidating key biological mechanisms in various contexts, including intrahepatic disease progression, interorgan crosstalk and systemic dysregulation. Furthermore, they are integral in developing novel therapeutics against MAFLD. However, substantial contextual variabilities exist across different models due to the lack of standardization in several aspects. As such, it is crucial to understand the strengths and weaknesses of existing models to better align them to the human condition. In this review, we consolidate the implications arising from the change in nomenclature and summarize MAFLD pathogenesis. Subsequently, we provide an updated evaluation of existing MAFLD preclinical models in alignment with the new definitions and perspectives to improve their translational relevance.https://www.mdpi.com/1422-0067/23/23/14762nonalcoholic fatty liver disease (NAFLD)nonalcoholic steatohepatitis (NASH)metabolic dysregulation-associated fatty liver disease (MAFLD)hepatic fibrosishepatocellular carcinoma (HCC)cardiovascular disease (CVD) |
| spellingShingle | Damien Chua Zun Siong Low Guo Xiang Cheam Aik Seng Ng Nguan Soon Tan Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm International Journal of Molecular Sciences nonalcoholic fatty liver disease (NAFLD) nonalcoholic steatohepatitis (NASH) metabolic dysregulation-associated fatty liver disease (MAFLD) hepatic fibrosis hepatocellular carcinoma (HCC) cardiovascular disease (CVD) |
| title | Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm |
| title_full | Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm |
| title_fullStr | Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm |
| title_full_unstemmed | Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm |
| title_short | Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm |
| title_sort | utility of human relevant preclinical animal models in navigating nafld to mafld paradigm |
| topic | nonalcoholic fatty liver disease (NAFLD) nonalcoholic steatohepatitis (NASH) metabolic dysregulation-associated fatty liver disease (MAFLD) hepatic fibrosis hepatocellular carcinoma (HCC) cardiovascular disease (CVD) |
| url | https://www.mdpi.com/1422-0067/23/23/14762 |
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