Horcas-Nieto 2023 Biochim Biophys Acta Mol Basis Dis

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Publications in the MiPMap
Horcas-Nieto JM, Versloot CJ, Langelaar-Makkinje M, Gerding A, Blokzijl T, Koster MH, Baanstra M, Martini IA, Coppes RP, Bourdon C, van Ijzendoorn SCD, Kim P, Bandsma RHJ, Bakker BM (2023) Organoids as a model to study intestinal and liver dysfunction in severe malnutrition. https://doi.org/10.1016/j.bbadis.2022.166635

Β» Biochim Biophys Acta Mol Basis Dis 1869:166635. PMID: 36581145 Open Access

Horcas-Nieto Jose M, Versloot Christian J, Langelaar-Makkinje Miriam, Gerding Albert, Blokzijl Tjasso, Koster Mirjam H, Baanstra Mirjam, Martini Ingrid A, Coppes Robert P, Bourdon Celine, van Ijzendoorn Sven CD, Kim Peter, Bandsma Robert HJ, Bakker Barbara M (2023) Biochim Biophys Acta Mol Basis Dis

Abstract: Hospitalized children with severe malnutrition face high mortality rates and often suffer from hepatic and intestinal dysfunction, with negative impacts on their survival. New treatments cannot be developed without understanding the underlying pathophysiology. We have established and characterized translational organoid models of severe malnutrition of the liver and the intestine. In these models, amino acid starvation recapitulates the expected organ-specific functional changes (e.g., hepatic steatosis, barrier dysfunction) accompanied by reduced mitochondrial and peroxisomal proteins, and altered intestinal tight junction proteins. Resupplementation of amino acids or pharmacological interventions with rapamycin or fenofibrate lead to partial recovery. Restoration of protein levels aligned with signs of improved peroxisomal function in both organoids, and increased mitochondrial proteins and tight junction protein claudin-3 in intestinal organoids. We present two organoid models as novel tools to gain mechanistic insights and to act as a testing platform for potential treatments for intestinal and hepatic dysfunction in severe malnutrition. β€’ Keywords: Amino acids, Malnutrition, Mitochondria, Organoids, Peroxisomes β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: NL Groningen Reijngoud RJ

Labels: MiParea: Respiration  Pathology: Other 

Organism: Mouse  Tissue;cell: Liver, Other cell lines 

Coupling state: LEAK, OXPHOS, ET  Pathway:HRR: Oxygraph-2k 


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