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Endothelial DLL4 Is an Adipose Depot–Specific Fasting Sensor Regulating Fatty Acid Fluxes

dc.rights.licenseopenen_US
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorAUPETIT, Alex
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorDECAUNES, Pauline
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorBELLES, Chloé
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorRIANT, Elodie
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorGALITZKY, Jean
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCHAPOULY, Candice
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorLAISNÉ, Margaux
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorFLORES-FLORES, Rémy
hal.structure.identifierService Chirurgie maxillo-faciale et plastique de la face [CHU Toulouse]
dc.contributor.authorCHAPUT, Benoit
hal.structure.identifierLaboratoires Clarins
dc.contributor.authorVIÉ, Katell
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorARNAL, Jean-François
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorBOULOUMIÉ, Anne
hal.structure.identifierInstitut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
dc.contributor.authorBRIOT, Anaïs
dc.date.accessioned2025-03-18T17:13:27Z
dc.date.available2025-03-18T17:13:27Z
dc.date.issued2023-05
dc.identifier.issn1079-5642en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/205537
dc.description.abstractEnBackground: Adaptation of fat depots to change in fuel availability is critical for metabolic flexibility and cardiometabolic health. The mechanisms responsible for fat depot-specific lipid sensing and shuttling remain elusive. Adipose tissue microvascular endothelial cells (AT-EC) regulates bidirectional fatty acid fluxes depending on fed or fasted state. How AT-EC sense and adapt to metabolic changes according to AT location remains to be established. Methods: We combined transcriptional analysis of native human AT-EC together with in vitro approaches in primary human AT-EC and in vivo and ex vivo studies of mice under fed and fasted conditions. Results: Transcriptional large-scale analysis of human AT-EC isolated from gluteofemoral and abdominal subcutaneous AT revealed that the endothelium exhibits a fat depot–specific signature associated with lipid handling and Notch signaling enrichment. We uncovered a functional link between metabolic status and endothelial DLL4 (delta-like canonical notch ligand 4), which decreases with fasting. DLL4 regulates fatty acid uptake through nontranscriptional modulation of macropinocytosis-dependent long chain fatty acid uptake. Importantly, the changes in DLL4 expression, in response to energy transition state, is impaired under obesogenic conditions, an early alteration coinciding with a defect in systemic fatty acid fluxes adaptation and a resistance to weight loss. Conclusions: DLL4 is a major actor in the adaptive mechanisms of AT-EC to regulate lipid fluxes. It likely contributes to fat depot-dependent metabolism in response to energy transition states. AT-EC alteration with obesity may favor metabolic inflexibility and the development of cardiometabolic disorders.
dc.language.isoENen_US
dc.subject.enadipocytes
dc.subject.encardiovascular diseases
dc.subject.endiet
dc.subject.enendocytosis
dc.subject.enlipids
dc.subject.enobesity
dc.subject.meshMice
dc.subject.meshHumans
dc.subject.meshAdaptor Proteins, Signal Transducing
dc.subject.meshSerpins
dc.subject.meshSkin
dc.subject.meshSkin Transplantation
dc.subject.meshAnimals
dc.subject.meshEndothelial Cells
dc.subject.meshFatty Acids
dc.subject.meshObesity
dc.subject.meshFasting
dc.subject.meshEndothelium
dc.subject.meshCardiovascular Diseases
dc.subject.meshCalcium-Binding Proteins
dc.title.enEndothelial DLL4 Is an Adipose Depot–Specific Fasting Sensor Regulating Fatty Acid Fluxes
dc.typeArticle de revueen_US
dc.identifier.doi10.1161/ATVBAHA.122.318876en_US
dc.subject.halSciences du Vivant [q-bio]en_US
dc.identifier.pubmed3692423en_US
bordeaux.journalArteriosclerosis, Thrombosis, and Vascular Biologyen_US
bordeaux.page684-696en_US
bordeaux.volume43en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires (BMC) - UMR 1034en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-04669324
hal.version1
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Arteriosclerosis,%20Thrombosis,%20and%20Vascular%20Biology&rft.date=2023-05&rft.volume=43&rft.issue=5&rft.spage=684-696&rft.epage=684-696&rft.eissn=1079-5642&rft.issn=1079-5642&rft.au=AUPETIT,%20Alex&DECAUNES,%20Pauline&BELLES,%20Chlo%C3%A9&RIANT,%20Elodie&GALITZKY,%20Jean&rft.genre=article


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