Author, as appears in the article.: Auguet, Teresa; Bertran, Laia; Binetti, Jessica; Aguilar, Carmen; Martinez, Salome; Guiu-Jurado, Esther; Sabench, Fatima; Adalid, Laia; Antonio Porras, Jose; Riesco, David; Del Castillo, Daniel; Richart, Cristobal;

Department: Medicina i Cirurgia

URV's Author/s: Aguilar Crespillo, Carmen Isabel / Auguet Quintillà, Maria Teresa / Binetti, Jessica Angela / Del Castillo Déjardin, Daniel / Martínez González, María Salomé / Porras Ledantes, Jose Antonio / Richart Jurado, Cristobal Manuel / Sabench Pereferrer, Fàtima

Keywords: Insulin-resistance Inhibition Fibrosis Differentiation Adaptive immunity

Abstract: Objective This cohort study aimed to explore the relationship between the Notch signaling pathway and the degree of nonalcoholic fatty liver disease (NAFLD). Moreover, this study intended to investigate whether this pathway is related to hepatic lipid metabolism and Toll-like receptors (TLRs). Methods This study used real-time polymerase chain reaction analysis to evaluate the hepatic expression level of all genes studied (Notch receptorsNOTCH1,NOTCH2,NOTCH3, andNOTCH4, transcription factorsHES1andHES5, and Hes-related repressor proteinsHEY1andHEY2) in hepatic tissue from two cohorts: women with severe obesity (n = 57) and normal liver structure (n = 20) or NAFLD (n = 37). Results In women with severe obesity and NAFLD, this study found downregulation of hepaticHES5expression. This expression correlated positively with the hepatic expression ofHES1,HEY1, andNOTCH3. This study also found a positive correlation betweenHES5expression and sterol regulatory element-binding protein 1c (SREBP1c) and betweenNOTCH3and several genes related to hepatic lipid metabolism (encoding liver X nuclear receptor alpha variant 1, farnesoid X nuclear receptor,SREBP1c, acetyl-CoA carboxylase 1, fatty acid synthase, peroxisome proliferator-activated receptor alpha, carnitine palmitoyltransferase 1, carnitineO-octanoyltransferase, ATP-binding cassette subfamily A member 1, and ATP-binding cassette subfamily G member 1). Finally, this study found a positive correlation betweenNOTCH2andTLR2,TLR4, andTLR9and a positive relationship betweenNOTCH1andTLR9. Conclusions Taken together, these findings suggest that hepatic expression of Notch proteins and ligands in relation to lipid metabolism pathways in the liver could have a role in NAFLD pathogenesis.

Thematic Areas: Saúde coletiva Psicología Nutrition and dietetics Nutrition & dietetics Nutrição Medicine (miscellaneous) Medicina iii Medicina ii Medicina i Interdisciplinar General medicine Farmacia Enfermagem Endocrinology, diabetes and metabolism Endocrinology & metabolism Endocrinology Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciência de alimentos Biotecnología

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: joseantonio.porras@urv.cat mariasalome.martinez@urv.cat cristobalmanuel.richart@urv.cat danieldel.castillo@urv.cat mariateresa.auguet@urv.cat carmenisabel.aguilar@urv.cat carmenisabel.aguilar@urv.cat fatima.sabench@urv.cat jessicaangela.binetti@estudiants.urv.cat

Author identifier: 0000-0001-6418-1822 0000-0001-6185-2889 0000-0003-0852-6739 0000-0003-0456-3102 0000-0001-7024-7824 0000-0003-0396-6428 0000-0002-4440-562X 0000-0002-4440-562X 0000-0002-9262-8756 0000-0001-9660-7752

Record's date: 2023-05-20

Papper version: info:eu-repo/semantics/acceptedVersion

Link to the original source: https://onlinelibrary.wiley.com/doi/10.1002/oby.22873

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Obesity. 28 (8): 1487-1493

APA: Auguet, Teresa; Bertran, Laia; Binetti, Jessica; Aguilar, Carmen; Martinez, Salome; Guiu-Jurado, Esther; Sabench, Fatima; Adalid, Laia; Antonio Porras (2020). Hepatocyte Notch Signaling Deregulation Related to Lipid Metabolism in Women with Obesity and Nonalcoholic Fatty Liver. Obesity, 28(8), 1487-1493. DOI: 10.1002/oby.22873

Article's DOI: 10.1002/oby.22873

Entity: Universitat Rovira i Virgili

Journal publication year: 2020

Publication Type: Journal Publications