Itemaren erregistro erraza erakusten du
Insights into the mechanism of action of the chlorophyll derivative 13-2-hydroxypheophytine a on reducing neutral lipid reserves in zebrafish larvae and mice adipocytes
dc.contributor.author | Carrasco del Amor, Ana María | |
dc.contributor.author | Hernández Bautista, René | |
dc.contributor.author | Ussar, Sigfried | |
dc.contributor.author | Cristobal Barragán, Susana | |
dc.contributor.author | Urbatzka, Ralph | |
dc.date.accessioned | 2024-05-07T16:42:05Z | |
dc.date.available | 2024-05-07T16:42:05Z | |
dc.date.issued | 2023-12 | |
dc.identifier.citation | European Journal of Pharmacology 960 : (2023) // Article ID 176158 | es_ES |
dc.identifier.issn | 1879-0712 | |
dc.identifier.issn | 0014-2999 | |
dc.identifier.uri | http://hdl.handle.net/10810/67651 | |
dc.description.abstract | Obesity is a worldwide epidemic and natural products may hold promise in its treatment. The chlorophyll derivative 13-2-hydroxypheophytine (hpa) was isolated in a screen with zebrafish larvae to identify lipid reducing molecules from cyanobacteria. However, the mechanisms underlying the lipid-reducing effects of hpa in zebrafish larvae remain poorly understood. Thus, investigating the mechanism of action of hpa and validation in other model organisms such as mice represents important initial steps. In this study, we identified 14 protein targets of hpa in zebrafish larvae by thermal proteome profiling, and selected two targets (malate dehydrogenase and pyruvate kinase) involved in cellular metabolism for further validation by enzymatic measurements. Our findings revealed a dose-dependent inhibition of pyruvate kinase by hpa exposure using protein extracts of zebrafish larvae in vitro, and in exposure experiments from 3 to 5 days post fertilization in vivo. Analysis of untargeted metabolomics of zebrafish larvae detected 940 mass peaks (66 increased, 129 decreased) and revealed that hpa induced the formation of various phospholipid species (phosphoinositol, phosphoethanolamine, phosphatidic acid). Inter-species validation showed that brown adipocytes exposed to hpa significantly reduced the size of lipid droplets, increased maximal mitochondrial respiratory capacity, and the expression of PPARy during adipocyte differentiation. In line with our data, previous work described that reduced pyruvate kinase activity lowered hepatic lipid content via reduced pyruvate and citrate, and improved mitochondrial function via phospholipids. Thus, our data provide new insights into the molecular mechanism underlying the lipid reducing activities of hpa in zebrafish larvae, and species overlapping functions in reduction of lipids. | es_ES |
dc.description.sponsorship | This work was financed by national funds through FCT (Portugal, ERA-MBT/0001/2015), BMBF 031B0306 (Germany), and FORMAS (Sweden, 2016-02004), within the framework of the European ERA-NET Marine Biotechnology project “CYANOBESITY—Cyanobacteria as a source of bioactive compounds with effects on obesity and obesity-related co-morbidities”. The research was additionally supported by the FCT strategic fund UIDB/04423/2020 and UIDP/04423/2020, and by the project ATLANTIDA (ref. NORTE-01-0145-FEDER-000040), supported by the Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement and through the European Regional Development Fund (ERDF), and IKERBASQUE, Basque Foundation for Science (S.C.); Basque Government Research Grant IT-971-16 and IT-476-22 (S.C.); Magnus Bergvalls Foundations (S.C.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | chlorophyll derivatives | es_ES |
dc.subject | brown adipocytes | es_ES |
dc.subject | zebrafish | es_ES |
dc.subject | anti-obesity activity | es_ES |
dc.subject | mechanism of action | es_ES |
dc.subject | thermal proteome profiling | es_ES |
dc.title | Insights into the mechanism of action of the chlorophyll derivative 13-2-hydroxypheophytine a on reducing neutral lipid reserves in zebrafish larvae and mice adipocytes | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.sciencedirect.com/science/article/pii/S0014299923006726 | es_ES |
dc.identifier.doi | 10.1016/j.ejphar.2023.176158 | |
dc.departamentoes | Fisiología | es_ES |
dc.departamentoeu | Fisiologia | es_ES |