Identification of novel targets in adipose tissue involved in non-alcoholic fatty liver disease progression

Lopez-Yus, Marta ; Lorente-Cebrian, Silvia (Universidad de Zaragoza) ; Del Moral-Bergos, Raquel ; Horndler, Carlos ; Garcia-Sobreviela, Maria Pilar ; Casamayor, Carmen (Universidad de Zaragoza) ; Sanz-Paris, Alejandro (Universidad de Zaragoza) ; Bernal-Monterde, Vanesa ; Arbones-Mainar, Jose M.

Resumen: Obesity 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.

Idioma: Inglés

DOI: 10.1096/fj.202200118RR

Año: 2022

Publicado en: FASEB JOURNAL 36, 8 (2022), e22429 [14 pp.]
ISSN: 0892-6638

Factor impacto JCR: 4.8 (2022)

Categ. JCR: BIOLOGY rank: 18 / 92 = 0.196 (2022) - Q1 - T1
Categ. JCR: CELL BIOLOGY rank: 82 / 191 = 0.429 (2022) - Q2 - T2
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 88 / 285 = 0.309 (2022) - Q2 - T1

Factor impacto CITESCORE: 9.8 - Biochemistry, Genetics and Molecular Biology (Q1)

Factor impacto SCIMAGO: 1.386 - Biochemistry (Q1) - Biotechnology (Q1) - Genetics (Q1) - Medicine (miscellaneous) (Q1) - Molecular Biology (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B03-20R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII PI17/02268

Tipo y forma: Article (PostPrint)

Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)
Área (Departamento): Área Cirugía (Dpto. Cirugía)