DataVXAdvanced SciencePaper
journal article·2024-09Open access

The LIDPAD Mouse Model Captures the Multisystem Interactions and Extrahepatic Complications in MASLD

Zun Siong Low, Damien Chua, Hong Sheng Cheng, Rachel Tee, Wei Ren Tan, Christopher Ball, Norliza Binte Esmail Sahib, Ser Sue Ng, Jing Qu, Yingzi Liu, Haiyu Hong, Chaonong Cai, Nandini Chilagondanahalli Lakshmi Rao, Aileen Wee, Mark Dhinesh Muthiah, Zoë Bichler, Barbara Mickelson, Mei Suen Kong, Vanessa Shiyun Tay, Zhuang Yan, Jiapeng Chen, Aik Seng Ng, Yun Sheng Yip, Marcus Ivan Gerard Vos, Nicole Ashley Tan, Dao Liang Lim, Debbie Xiu En Lim, Manesh Chittezhath, Jadegoud Yaligar, Sanjay Kumar Verma, Harish Poptani, Xue Li Guan, Sambasivam Sendhil Velan, Yusuf Ali, Liang Li, Nguan Soon Tan, Walter Wahli

Advanced Science· Volume 11· Issue 35
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Abstract

Abstract 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.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Liver Disease Diagnosis and Treatment · Diet and metabolism studies · Adipose Tissue and Metabolism

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Lee Kong Chian School of Medicine Nanyang Technological University Singapore Clinical Sciences Building, 11 Mandalay Road Singapore 308232 Singapore

Metabolic Imaging Group Institute of Bioengineering and Bioimaging Agency for Science Technology and Research (A*STAR) 11 Biopolis Way Singapore 138667 Singapore

Department of Pathogen Biology Shenzhen Center for Disease Control and Prevention Shenzhen 518055 China

Intervention and Cell Therapy Center Peking University Shenzhen Hospital Shenzhen 518036 China

Department of Otolaryngology Head and Neck Surgery The Fifth Affiliated Hospital of Sun Yat‐sen University 52 Mei Hua East Road Zhuhai 519000 China

Department of Pathology Tan Tock Seng Hospital 11 Jalan Tan Tock Seng Singapore 308433 Singapore

Department of Pathology National University Hospital 5 Lower Kent Ridge Rd Singapore 119074 Singapore

Department of Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore

Division of Gastroenterology and Hepatology Department of Medicine National University Hospital Singapore 119074 Singapore

National University Centre for Organ Transplantation National University Health System Singapore 119074 Singapore

ENVIGO Madison WI 53713 USA

Radcliffe Department of Medicine John Radcliffe Hospital University of Oxford Oxford OX3 9DU UK

School of Biological Sciences Nanyang Technological University Singapore 60 Nanyang Drive Singapore 637551 Singapore

Singapore Institute for Clinical Sciences A*STAR 30 Medical Drive Singapore 117609 Singapore

Centre for Preclinical Imaging Institute of Systems Molecular & Integrative Biology University of Liverpool Biosciences Building, Crown Street Liverpool L69 7BE UK

Singapore Eye Research Institute (SERI) Singapore General Hospital Singapore 168751 Singapore

Department of Pharmacology School of Medicine Southern University of Science and Technology Shenzhen 518055 China

Institut national de recherche pour l'agriculture l'alimentation et l'environnement (INRAE) Toxalim (Research Centre in Food Toxicology) 180 Chemin de Tournefeuille Toulouse 1331 France

Center for Integrative Genomics Université de Lausanne Le Génopode Lausanne 1015 Switzerland

Funding

Ministry of Education - Singapore

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