000129950 001__ 129950
000129950 005__ 20240122154815.0
000129950 0247_ $$2doi$$a10.1016/j.jnutbio.2023.109503
000129950 0248_ $$2sideral$$a136254
000129950 037__ $$aART-2024-136254
000129950 041__ $$aeng
000129950 100__ $$aSánchez-Marco, Javier
000129950 245__ $$aThioredoxin domain containing 5 is involved in the hepatic storage of squalene into lipid droplets in a sex-specific way
000129950 260__ $$c2024
000129950 5060_ $$aAccess copy available to the general public$$fUnrestricted
000129950 5203_ $$aHepatic thioredoxin domain-containing 5 (TXNDC5) is a member of the protein disulfide isomerase family found associated with anti-steatotic properties of squalene and located in the endoplasmic reticulum and in lipid droplets. Considering that the latter are involved in hepatic squalene accumulation, the present research was aimed to investigate the role of TXNDC5 on hepatic squalene management in mice and in the AML12 hepatic cell line. Wild-type and TXNDC5-deficient (KO) mice were fed Western diets with or without 1% squalene supplementation for 6 weeks. In males, but not in females, absence of TXNDC5 blocked hepatic, but not duodenal, squalene accumulation. Hepatic lipid droplets were isolated and characterized using label-free LC-MS/MS analysis. TXNDC5 accumulated in this subcellular compartment of mice receiving squalene and was absent in TXNDC5-KO male mice. The latter mice were unable to store squalene in lipid droplets. CALR and APMAP were some of the proteins that responded to the squalene administration in all studied conditions. CALR and APMAP were positively associated with lipid droplets in the presence of squalene and they were decreased by the absence of TXNDC5. The increased squalene content was reproduced in vitro using AML12 cells incubated with squalene-loaded nanoparticles and this effect was not observed in an engineered cell line lacking TXNDC5. The phenomenon was also present when incubated in the presence of a squalene epoxidase inhibitor, suggesting a mechanism of squalene exocytosis involving CALR and APMAP. In conclusion, squalene accumulation in hepatic lipid droplets is sex-dependent on TXNDC5 that blocks its secretion.
000129950 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B16-23R$$9info:eu-repo/grantAgreement/ES/ISCIII-CIBERObn/CB06-03-1012$$9info:eu-repo/grantAgreement/ES/MICINN AEI/PID2019-104915RB-I00$$9info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-104915RB-I00
000129950 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttp://creativecommons.org/licenses/by-nc/3.0/es/
000129950 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000129950 700__ $$aBidooki, Seyed Hesamoddin$$uUniversidad de Zaragoza
000129950 700__ $$aAbuobeid, Roubi
000129950 700__ $$0(orcid)0000-0002-8442-8041$$aBarranquero, Cristina
000129950 700__ $$aHerrero-Continente, Tania
000129950 700__ $$aArnal, Carmen
000129950 700__ $$0(orcid)0000-0002-8100-5596$$aMartínez-Beamonte, Roberto$$uUniversidad de Zaragoza
000129950 700__ $$aLasheras, Roberto
000129950 700__ $$0(orcid)0000-0002-5841-0462$$aSurra, Joaquín C.$$uUniversidad de Zaragoza
000129950 700__ $$0(orcid)0000-0002-0108-1004$$aNavarro, María A.$$uUniversidad de Zaragoza
000129950 700__ $$0(orcid)0000-0002-3595-7668$$aRodríguez-Yoldi, María J.$$uUniversidad de Zaragoza
000129950 700__ $$0(orcid)0000-0003-3165-0156$$aArruebo, Manuel$$uUniversidad de Zaragoza
000129950 700__ $$0(orcid)0000-0002-6873-5244$$aSebastian, Victor$$uUniversidad de Zaragoza
000129950 700__ $$0(orcid)0000-0002-8251-8457$$aOsada, Jesús$$uUniversidad de Zaragoza
000129950 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000129950 7102_ $$15005$$2555$$aUniversidad de Zaragoza$$bDpto. Ing.Quím.Tecnol.Med.Amb.$$cÁrea Ingeniería Química
000129950 7102_ $$12008$$2700$$aUniversidad de Zaragoza$$bDpto. Produc.Animal Cienc.Ali.$$cÁrea Producción Animal
000129950 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000129950 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000129950 773__ $$g124, 109503 [13 pp.] (2024), 109503$$pJ. nutr. biochem.$$tJournal of Nutritional Biochemistry$$x0955-2863
000129950 8564_ $$s4173512$$uhttps://zaguan.unizar.es/record/129950/files/texto_completo.pdf$$yVersión publicada
000129950 8564_ $$s2631735$$uhttps://zaguan.unizar.es/record/129950/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000129950 909CO $$ooai:zaguan.unizar.es:129950$$particulos$$pdriver
000129950 951__ $$a2024-01-22-15:36:17
000129950 980__ $$aARTICLE