<div class="csl-bib-body">
<div class="csl-entry">Pfleger, R., Tomin, T., Schittmayer-Schantl, M., & Birner-Grünberger, R. (2025, September 12). <i>From Dormant to Dynamic: Unravelling the Role of Lipolysis in Hepatic Stellate Cell Activation</i> [Poster Presentation]. APMRS 2025, Austria. http://hdl.handle.net/20.500.12708/221392</div>
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dc.identifier.uri
http://hdl.handle.net/20.500.12708/221392
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dc.description.abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) encompasses a spectrum of progressive liver disorders that, if unresolved, can trigger inflammation and fibrosis. Hepatic stellate cells (HSCs) are key mediators of these fibrotic processes in the liver. In healthy tissue they store large amounts of lipids, primarily retinol esters (RE) and triacylglycerols (TAGs) in intracellular lipid droplets (LDs). Upon liver injury or chronic inflammation quiescent HSCs transdifferentiate into “activated” myofibroblast-like cells. Hallmark features of activated HSCs include increased proliferative capacity, directed migration towards injury sites and increased secretion of extracellular matrix proteins (scar tissue). However, the most prominent change is the shift in LD phenotype from large, RE-rich droplets to more dynamic, smaller LDs enriched in polyunsaturated fatty acid (PUFA)-containing TAGs. Understanding the mechanisms involved in HSC transdifferentiating is crucial for targeting liver fibrosis and its progression to more severe conditions.
To address this, we compared proteomes of pseudo-quiescent and activated LX-2 cells (an immortalized human HSC line) by label-free quantitative (LFQ) proteomics and evaluated serine hydrolase activity via activity-based protein profiling (ABPP) to probe metabolic pathway alterations. The diverse enzyme superfamily of serine hydrolases encompasses many key lipases likely involved in LD remodelling. To dissect the specific contribution of neutral lipolysis, we pharmacologically inhibited ATGL – the rate-limiting enzyme of the lipolytic cascade – and assessed its effects on both pseudo-quiescent and activated HSCs.
To date, our results demonstrate that while the protein level of key serine hydrolases (e.g., ATGL) remained unchanged, their enzymatic activities were significantly modulated during activation. Inhibition of ATGL abrogated LD remodelling, underscoring its essential role in this process. In contrast, overall HSC activation was only modestly affected by impaired lipid hydrolysis, suggesting that LD remodelling may be a consequence rather than a prerequisite of HSC activation.
Our findings elucidate ATGL’s pivotal function in LD dynamics during HSC activation and offer new insights into our understanding of lipid hydrolysis in HSC activation.
en
dc.description.sponsorship
FWF - Österr. Wissenschaftsfonds
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dc.language.iso
en
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dc.subject
hepatic stellate cells
en
dc.subject
activation
en
dc.subject
proteomics
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dc.subject
lipid hydrolases
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dc.subject
liver fibrosis
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dc.title
From Dormant to Dynamic: Unravelling the Role of Lipolysis in Hepatic Stellate Cell Activation
en
dc.type
Presentation
en
dc.type
Vortrag
de
dc.contributor.affiliation
TU Wien (Vienna, AT)
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dc.relation.grantno
F 7309-B21
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dc.type.category
Poster Presentation
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tuw.project.title
Lipidhydrolyse im Krebs und in Lipid-assoziierten Krankheiten
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tuw.researchinfrastructure
Cell Culture Core Facility (CCCF)
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tuw.researchTopic.id
X1
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tuw.researchTopic.name
Beyond TUW-research focus
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tuw.researchTopic.value
100
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tuw.publication.orgunit
E164-01-3 - Forschungsgruppe Bioanalytik
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tuw.publication.orgunit
E056-12 - Fachbereich ENROL DP
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tuw.author.orcid
0009-0001-3402-2043
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tuw.author.orcid
0000-0002-7071-2316
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tuw.author.orcid
0000-0003-3249-655X
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tuw.author.orcid
0000-0003-3950-0312
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tuw.event.name
APMRS 2025
en
tuw.event.startdate
12-09-2025
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tuw.event.enddate
13-09-2025
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tuw.event.online
On Site
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tuw.event.type
Event for scientific audience
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tuw.event.country
AT
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tuw.event.institution
APMA, TU Wien
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tuw.event.presenter
Pfleger, Raphael
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tuw.event.track
Single Track
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wb.sciencebranch
Chemie
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wb.sciencebranch
Biologie
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wb.sciencebranch
Anatomie, Pathologie, Physiologie
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wb.sciencebranch.oefos
1040
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wb.sciencebranch.oefos
1060
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wb.sciencebranch.oefos
3011
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wb.sciencebranch.value
50
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wb.sciencebranch.value
20
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wb.sciencebranch.value
30
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item.openairetype
conference poster not in proceedings
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item.openairecristype
http://purl.org/coar/resource_type/c_18co
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item.cerifentitytype
Publications
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item.languageiso639-1
en
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item.grantfulltext
none
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item.fulltext
no Fulltext
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crisitem.author.dept
TU Wien (Vienna, AT)
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crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
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crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
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crisitem.author.dept
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
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crisitem.author.orcid
0009-0001-3402-2043
-
crisitem.author.orcid
0000-0002-7071-2316
-
crisitem.author.orcid
0000-0003-3249-655X
-
crisitem.author.orcid
0000-0003-3950-0312
-
crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
-
crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
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crisitem.author.parentorg
E164 - Institut für Chemische Technologien und Analytik
