The LIDPAD mouse model captures the multisystem interactions and extrahepatic complications in MASLD
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| Názov: | The LIDPAD mouse model captures the multisystem interactions and extrahepatic complications in MASLD |
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| Autori: | Low, Zun Siong, Chua, Damien, Cheng, Hong Sheng, Tee, Rachel, Tan, Wei Ren, Ball, Christopher, Norliza Binte Esmail Sahib, Ng, Ser Sue, Qu, Jing, Liu, Yingzi, Hong, Haiyu, Cai, Chaonong, Rao, Nandini Chilagondanahalli Lakshmi, Wee, Aileen, Muthiah, Mark Dhinesh, Bichler, Zoë, Mickelson, Barbara, Kong, Mei Suen, Tay, Vanessa Shiyun, Yan, Zhuang, Chen, Jiapeng, Ng, Aik Seng, Yip, Yun Sheng, Vos, Marcus Ivan Gerard, Tan, Nicole Ashley, Lim, Dao Liang, Lim, Debbie Xiu En, Chittezhath, Manesh, Yaligar, Jadegoud, Verma, Sanjay Kumar, Poptani, Harish, Guan, Xue Li, Velan, Sambasivam Sendhil, Ali, Yusuf, Li, Liang, Tan, Nguan Soon, Wahli, Walter |
| Prispievatelia: | Lee Kong Chian School of Medicine (LKCMedicine), School of Biological Sciences |
| Rok vydania: | 2024 |
| Zbierka: | DR-NTU (Digital Repository at Nanyang Technological University, Singapore) |
| Predmety: | Medicine, Health and Life Sciences, Diet-induced weight loss, Gut microbiome |
| Popis: | Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut-liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut-pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic-guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease-associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development. ; Ministry of Education (MOE) ; Nanyang Technological University ; Published version ; This research was supported by the following: NTUitive SPARK program (WW), Lee Kong Chian School of Medicine, Nanyang Technological University Singapore Start-Up Grant (WW). Ferring Singapore Innovation grant (WW, NST), Singapore Ministry of Education under its Singapore Ministry of Education Academic Research Fund Tier 1 (RG30/20) (NST) and ... |
| Druh dokumentu: | article in journal/newspaper |
| Popis súboru: | application/pdf |
| Jazyk: | English |
| Relation: | SPARK; NTU SUG; RG30/20; MOE2017-T2-1-038; Advanced Science; https://hdl.handle.net/10356/180405; 35; 11; e2404326 |
| DOI: | 10.1002/advs.202404326 |
| Dostupnosť: | https://hdl.handle.net/10356/180405 https://doi.org/10.1002/advs.202404326 |
| Rights: | © 2024 The Author(s). Advanced Science published by Wiley-VCHGmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Prístupové číslo: | edsbas.974DF517 |
| Databáza: | BASE |
Nájsť tento článok vo Web of Science | Abstrakt: | Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut-liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut-pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic-guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease-associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development. ; Ministry of Education (MOE) ; Nanyang Technological University ; Published version ; This research was supported by the following: NTUitive SPARK program (WW), Lee Kong Chian School of Medicine, Nanyang Technological University Singapore Start-Up Grant (WW). Ferring Singapore Innovation grant (WW, NST), Singapore Ministry of Education under its Singapore Ministry of Education Academic Research Fund Tier 1 (RG30/20) (NST) and ... |
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| DOI: | 10.1002/advs.202404326 |