000131655 001__ 131655
000131655 005__ 20241125101150.0
000131655 0247_ $$2doi$$a10.1152/ajpcell.00291.2023
000131655 0248_ $$2sideral$$a136325
000131655 037__ $$aART-2023-136325
000131655 041__ $$aeng
000131655 100__ $$aLopez-Yus, Marta
000131655 245__ $$aCRISPR/Cas9-mediated deletion of adipocyte genes associated with NAFLD alters adipocyte lipid handling and reduces steatosis in hepatocytes in vitro
000131655 260__ $$c2023
000131655 5203_ $$aObesity is a major risk factor for the development of nonalcoholic fatty liver disease (NAFLD), and the subcutaneous white adi-pose tissue (scWAT) is the primary lipid storage depot and regulates lipidfluxes to other organs. Our previous work identifiedgenes upregulated in scWAT of patients with NAFLD:SOCS3,DUSP1,andSIK1. Herein, we knocked down (KD) their expres-sion in human adipose-derived mesenchymal stem cells (hADMSCs) using clustered regularly interspaced short palindromicrepeats (CRISPR)/Cas9 technology and characterized their phenotype. We found thatSOCS3,DUSP1,andSIK1expression inhADMSC-derived adipocytes was not critical for adipogenesis. However, the metabolic characterization of the cells suggestedthat the genes played important roles in lipid metabolism. Reduction ofSIK1expression significantly increased both de novolipogenesis (DNL) and palmitate-induced lipogenesis (PIL). Editing outSOCS3reduced DNL while increasing isoproterenol-induced lipolysis and insulin-induced palmitate accumulation. Conversely,DUSP1reduced PIL and DNL. Moreover, RNA-sequencing analysis of edited cells showed that these genes not only altered lipid metabolism but also other biological path-ways related to inflammatory processes, in the case ofDUSP1, extracellular matrix remodeling forSOCS3, or cellular transportforSIK1. Finally, to evaluate a possible adipocyte-hepatocyte axis, human hepatoma HepG2 cells were cocultured with editedhADMSCs-derived adipocytes in the presence of [3H]-palmitate. All HepG2 cells cultured with DUSP1-, SIK1-, or SOCS3-KD adi-pocytes decreased [3H]-palmitate accumulation compared with control adipocytes. These results support our hypotheses thatSOCS3,DUSP1,andSIK1regulate multiple aspects of adipocyte function, which may play a role in the progression of obesity-associated comorbidities, such as NAFLD.
000131655 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B03-23R$$9info:eu-repo/grantAgreement/ES/ISCIII/PI22-01366$$9info:eu-repo/grantAgreement/ES/MICINN /BFU2015-65937-R$$9info:eu-repo/grantAgreement/ES/UZ/JIUZ-2021-BIO-03
000131655 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000131655 590__ $$a5.0$$b2023
000131655 592__ $$a1.711$$b2023
000131655 591__ $$aPHYSIOLOGY$$b8 / 85 = 0.094$$c2023$$dQ1$$eT1
000131655 593__ $$aPhysiology$$c2023$$dQ1
000131655 591__ $$aCELL BIOLOGY$$b66 / 205 = 0.322$$c2023$$dQ2$$eT1
000131655 593__ $$aCell Biology$$c2023$$dQ1
000131655 594__ $$a9.1$$b2023
000131655 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000131655 700__ $$aFrendo-Cumbo, Scott
000131655 700__ $$adel Moral-Bergos, Raquel
000131655 700__ $$aGarcia-Sobreviela, Maria Pilar
000131655 700__ $$aBernal-Monterde, Vanesa$$uUniversidad de Zaragoza
000131655 700__ $$aRydén, Mikael
000131655 700__ $$0(orcid)0000-0002-1033-6152$$aLorente-Cebrian, Silvia$$uUniversidad de Zaragoza
000131655 700__ $$aArbones-Mainar, Jose M.
000131655 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000131655 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000131655 773__ $$g325, 5 (2023), C1178-C1189$$pAm. j. physiol., Cell physiol.$$tAmerican Journal of Physiology - Cell Physiology$$x0363-6143
000131655 8564_ $$s2354451$$uhttps://zaguan.unizar.es/record/131655/files/texto_completo.pdf$$yVersión publicada
000131655 8564_ $$s3160522$$uhttps://zaguan.unizar.es/record/131655/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000131655 909CO $$ooai:zaguan.unizar.es:131655$$particulos$$pdriver
000131655 951__ $$a2024-11-22-12:06:32
000131655 980__ $$aARTICLE