<div class="csl-bib-body">
<div class="csl-entry">Reindl, S., Honeder, S. E., Pirchheim, A., Bigl, G., Gosset, E., Bradic, I., Kuentzel, K. B., Grabner, G., Kratky, D., Schittmayer-Schantl, M., & Birner-Grünberger, R. (2025, June 16). <i>Competitive activity-based protein profiling reveals tissue-specific off-targets of widely used lipase inhibitors</i> [Poster Presentation]. EUPA 2025, Saint-Malo, France.</div>
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Dysregulation of lipid hydrolases contributes to diseases such as obesity, cardiovascular and central nervous system disorders and metabolic syndromes. Lipase inhibitors are employed clinically to treat these conditions and as experimental tools to study the physiological and pathological roles of lipases. However, off-target effects in both research and therapy applications can compromise full target selectivity and confound outcomes. To address this, we applied competitive activity-based protein profiling (ABPP) to identify novel lipase inhibitor off-targets. Using a serine hydrolase-targeting probe in combination with inhibitors of the lipolytic enzymes Adipose Triglyceride Lipase (ATGL), Hormone Sensitive Lipase (HSL), Monoacylglycerol Lipase (MGL) or Lysosomal Acid Lipase (LAL), we analyzed LX-2 human hepatic stellate cells, murine liver tissue, murine primary hepatocytes as well as bone marrow-derived macrophages (BMDM). This method revealed several known as well as some unknown off-targets of HSL inhibitor Hi 76-0079, MGL inhibitors JZL-184 and Lu AG06466 as well as LAL inhibitors Lalistat-1 and Lalistat-2. We further observe differences in the lipase activity profiles between hepatocytes and BMDM. In conclusion, our competitive ABPP-based approach uncovers tissue-specific off-targets of prominent lipase inhibitors, highlighting their potential effects on cellular function and the importance of tissue context in lipase inhibition studies.
en
dc.description.sponsorship
FWF - Österr. Wissenschaftsfonds
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dc.description.sponsorship
FWF - Österr. Wissenschaftsfonds
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dc.language.iso
en
-
dc.subject
competitive activity-based proteomics
en
dc.subject
lipase
en
dc.subject
lipase inhibitors
en
dc.title
Competitive activity-based protein profiling reveals tissue-specific off-targets of widely used lipase inhibitors
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dc.type
Presentation
en
dc.type
Vortrag
de
dc.contributor.affiliation
Medical University of Graz, Austria
-
dc.contributor.affiliation
TU Wien, Austria
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dc.contributor.affiliation
TU Wien, Austria
-
dc.contributor.affiliation
Medical University of Graz, Austria
-
dc.contributor.affiliation
Medical University of Graz, Austria
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dc.relation.grantno
F 7309-B21
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dc.relation.grantno
COE 7
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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.project.title
COE Microbiomes drive Planetary Health
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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
-
tuw.researchTopic.value
100
-
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
0009-0000-6859-6902
-
tuw.author.orcid
0000-0002-7110-9957
-
tuw.author.orcid
0000-0003-1357-7573
-
tuw.author.orcid
0000-0003-3249-655X
-
tuw.author.orcid
0000-0003-3950-0312
-
tuw.event.name
EUPA 2025
en
tuw.event.startdate
16-06-2025
-
tuw.event.enddate
20-06-2025
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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.place
Saint-Malo
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tuw.event.country
FR
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tuw.event.institution
EUPA
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tuw.event.presenter
Reindl, Sarah
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wb.sciencebranch
Chemie
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wb.sciencebranch.oefos
1040
-
wb.sciencebranch.value
100
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item.languageiso639-1
en
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item.openairetype
conference poster not in proceedings
-
item.openairecristype
http://purl.org/coar/resource_type/c_18co
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item.grantfulltext
none
-
item.cerifentitytype
Publications
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item.fulltext
no Fulltext
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crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
-
crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
-
crisitem.author.dept
Medical University of Graz, Austria
-
crisitem.author.dept
TU Wien, Austria
-
crisitem.author.dept
TU Wien, Austria
-
crisitem.author.dept
Medical University of Graz, Austria
-
crisitem.author.dept
Medical University of Graz, Austria
-
crisitem.author.dept
E164-01-3 - Forschungsgruppe Bioanalytik
-
crisitem.author.dept
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
-
crisitem.author.orcid
0009-0000-6859-6902
-
crisitem.author.orcid
0000-0002-7110-9957
-
crisitem.author.orcid
0000-0003-1357-7573
-
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
-
crisitem.author.parentorg
E164-01 - Forschungsbereich Imaging und Instrumentelle Analytische Chemie
-
crisitem.author.parentorg
E164 - Institut für Chemische Technologien und Analytik
