Related Experiment Video
Updated: Jul 10, 2026
12:40
Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery
Published on: May 19, 2018
Innovative models to explore hepatic involvement in Prader-Willi syndrome
Romar Guintu Dabban1,2,3, Graziano Grugni4, Adele Bondesan4
1Fondazione Italiana Fegato (Italian Liver Foundation), Innovative Models Unit, Trieste, Italy.
Frontiers in Endocrinology
|July 9, 2026
Summary
Prader-Willi syndrome (PWS) involves unique metabolic changes, with impaired lipid handling affecting liver health despite obesity. Induced pluripotent stem cell models offer insights into PWS mechanisms and potential therapies.
Area of Science:
- Genetics
- Metabolic Disorders
- Hepatology
Background:
- Prader-Willi syndrome (PWS) is a rare neurodevelopmental disorder with complex metabolic features, including obesity and altered lipid metabolism.
- PWS exhibits an unusual metabolic profile with extreme adiposity but a lower risk of insulin resistance and hepatic complications.
- Genetic factors in PWS impair adipocyte lipid handling, impacting hepatic lipid burden and potentially influencing steatosis risk.
Purpose of the Study:
- To investigate the distinct metabolic signature and hepatic involvement in Prader-Willi syndrome.
- To explore the role of intrinsic lipid handling and endocrine signaling in PWS-related liver issues.
- To highlight the utility of induced pluripotent stem cell (iPSC)-derived models for studying PWS.
Main Methods:
- Systemic lipidomic and metabolomic profiling to identify metabolic signatures.
- Analysis of hepatic lipid handling and endocrine signaling pathways in PWS.
- Utilizing hepatocyte-like cells (HLCs) and iPSC-derived organoids as models for PWS research.
Main Results:
- PWS displays a unique metabolic signature with altered circulating phospholipids.
- Hepatic involvement in PWS is primarily driven by intrinsic lipid handling defects, not solely adiposity.
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is less common in PWS.
Conclusions:
- iPSC-derived models (HLCs, organoids) are crucial for dissecting PWS mechanisms, bridging molecular and organismal levels.
- These models facilitate understanding patient-specific epigenetic regulation and tissue-specific metabolic dysfunction in PWS.
- Advanced mechanistic understanding and therapeutic development for PWS can be achieved using these innovative stem cell-based strategies.
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