000118857 001__ 118857
000118857 005__ 20240319081021.0
000118857 0247_ $$2doi$$a10.1096/fj.202200118RR
000118857 0248_ $$2sideral$$a129610
000118857 037__ $$aART-2022-129610
000118857 041__ $$aeng
000118857 100__ $$aLopez-Yus, Marta
000118857 245__ $$aIdentification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression
000118857 260__ $$c2022
000118857 5060_ $$aAccess copy available to the general public$$fUnrestricted
000118857 5203_ $$aObesity is a major risk factor for the development of Nonalcoholic fatty liver disease (NAFLD). We hypothesize that a dysfunctional subcutaneous white adipose tissue (scWAT) may lead to an accumulation of ectopic fat in the liver. Our aim was to investigate the molecular mechanisms involved in the causative role of scWAT in NALFD progression. We performed a RNA-sequencing analysis in a discovery cohort (n = 45) to identify genes in scWAT correlated with fatty liver index, a qualitative marker of liver steatosis. We then validated those targets in a second cohort (n = 47) of obese patients who had liver biopsies available. Finally, we obtained scWAT mesenchymal stem cells (MSCs) from 13 obese patients at different stages of NAFLD and established in vitro models of human MSC (hMSC)-derived adipocytes. We observed impaired adipogenesis in hMSC-derived adipocytes as liver steatosis increased, suggesting that an impaired adipogenic capacity is a critical event in the development of NAFLD. Four genes showed a differential expression pattern in both scWAT and hMSC-derived adipocytes, where their expression paralleled steatosis degree: SOCS3, DUSP1, SIK1, and GADD45B. We propose these genes as key players in NAFLD progression. They could eventually constitute potential new targets for future therapies against liver steatosis.
000118857 536__ $$9info:eu-repo/grantAgreement/ES/ISCIII PI17/02268$$9info:eu-repo/grantAgreement/ES/DGA/B03-20R
000118857 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000118857 590__ $$a4.8$$b2022
000118857 592__ $$a1.386$$b2022
000118857 591__ $$aBIOLOGY$$b18 / 92 = 0.196$$c2022$$dQ1$$eT1
000118857 593__ $$aBiochemistry$$c2022$$dQ1
000118857 591__ $$aCELL BIOLOGY$$b82 / 191 = 0.429$$c2022$$dQ2$$eT2
000118857 593__ $$aBiotechnology$$c2022$$dQ1
000118857 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b88 / 285 = 0.309$$c2022$$dQ2$$eT1
000118857 593__ $$aGenetics$$c2022$$dQ1
000118857 593__ $$aMedicine (miscellaneous)$$c2022$$dQ1
000118857 593__ $$aMolecular Biology$$c2022$$dQ2
000118857 594__ $$a9.8$$b2022
000118857 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000118857 700__ $$0(orcid)0000-0002-1033-6152$$aLorente-Cebrian, Silvia$$uUniversidad de Zaragoza
000118857 700__ $$aDel Moral-Bergos, Raquel
000118857 700__ $$aHorndler, Carlos
000118857 700__ $$aGarcia-Sobreviela, Maria Pilar
000118857 700__ $$aCasamayor, Carmen$$uUniversidad de Zaragoza
000118857 700__ $$0(orcid)0000-0002-7758-3588$$aSanz-Paris, Alejandro$$uUniversidad de Zaragoza
000118857 700__ $$aBernal-Monterde, Vanesa
000118857 700__ $$0(orcid)0000-0002-8982-3737$$aArbones-Mainar, Jose M.
000118857 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000118857 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000118857 7102_ $$11013$$2090$$aUniversidad de Zaragoza$$bDpto. Cirugía$$cÁrea Cirugía
000118857 773__ $$g36, 8 (2022), e22429 [14 pp.]$$pFASEB j.$$tFASEB JOURNAL$$x0892-6638
000118857 8564_ $$s384226$$uhttps://zaguan.unizar.es/record/118857/files/texto_completo.pdf$$yPreprint
000118857 8564_ $$s1412412$$uhttps://zaguan.unizar.es/record/118857/files/texto_completo.jpg?subformat=icon$$xicon$$yPreprint
000118857 909CO $$ooai:zaguan.unizar.es:118857$$particulos$$pdriver
000118857 951__ $$a2024-03-18-16:13:43
000118857 980__ $$aARTICLE