dc.contributor.author
Holzhütter, Hermann-Georg
dc.contributor.author
Berndt, Nikolaus
dc.date.accessioned
2021-09-10T09:37:32Z
dc.date.available
2021-09-10T09:37:32Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/31915
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-31647
dc.description.abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common type of chronic liver disease in developed nations, affecting around 25% of the population. Elucidating the factors causing NAFLD in individual patients to progress in different rates and to different degrees of severity, is a matter of active medical research. Here, we aim to provide evidence that the intra-hepatic heterogeneity of rheological, metabolic and tissue-regenerating capacities plays a central role in disease progression. We developed a generic mathematical model that constitutes the liver as ensemble of small liver units differing in their capacities to metabolize potentially cytotoxic free fatty acids (FFAs) and to repair FFA-induced cell damage. Transition from simple steatosis to more severe forms of NAFLD is described as self-amplifying process of cascading liver failure, which, to stop, depends essentially on the distribution of functional capacities across the liver. Model simulations provided the following insights: (1) A persistently high plasma level of FFAs is sufficient to drive the liver through different stages of NAFLD; (2) Presence of NAFLD amplifies the deleterious impact of additional tissue-damaging hits; and (3) Coexistence of non-steatotic and highly steatotic regions is indicative for the later occurrence of severe NAFLD stages.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
mathematical model
en
dc.subject
non-alcoholic liver disease (NAFLD)
en
dc.subject
lipotoxicity
en
dc.subject
tissue damage
en
dc.subject
liver regeneration
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Computational Hypothesis: How Intra-Hepatic Functional Heterogeneity May Influence the Cascading Progression of Free Fatty Acid-Induced Non-Alcoholic Fatty Liver Disease (NAFLD)
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
578
dcterms.bibliographicCitation.doi
10.3390/cells10030578
dcterms.bibliographicCitation.journaltitle
Cells
dcterms.bibliographicCitation.number
3
dcterms.bibliographicCitation.originalpublishername
MDPI AG
dcterms.bibliographicCitation.volume
10
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
33808045
dcterms.isPartOf.eissn
2073-4409