Thioredoxin domain containing 5 is involved in the hepatic storage of squalene into lipid droplets in a sex-specific way
Sánchez-Marco, Javier ; Bidooki, Seyed Hesamoddin (Universidad de Zaragoza) ; Abuobeid, Roubi ; Barranquero, Cristina ; Herrero-Continente, Tania ; Arnal, Carmen ; Martínez-Beamonte, Roberto (Universidad de Zaragoza) ; Lasheras, Roberto ; Surra, Joaquín C. (Universidad de Zaragoza) ; Navarro, María A. (Universidad de Zaragoza) ; Rodríguez-Yoldi, María J. (Universidad de Zaragoza) ; Arruebo, Manuel (Universidad de Zaragoza) ; Sebastian, Victor (Universidad de Zaragoza) ; Osada, Jesús (Universidad de Zaragoza)
Resumen: Hepatic 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.
Idioma: Inglés
DOI: 10.1016/j.jnutbio.2023.109503
Año: 2024
Publicado en: Journal of Nutritional Biochemistry 124, 109503 [13 pp.] (2024), 109503
ISSN: 0955-2863
Factor impacto JCR: 4.9 (2024)
Categ. JCR: NUTRITION & DIETETICS rank: 18 / 112 = 0.161 (2024) - Q1 - T1
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 72 / 319 = 0.226 (2024) - Q1 - T1
Factor impacto SCIMAGO: 1.28 - Biochemistry (Q1) - Endocrinology, Diabetes and Metabolism (Q1) - Nutrition and Dietetics (Q1) - Clinical Biochemistry (Q1) - Molecular Biology (Q2)
Financiación: info:eu-repo/grantAgreement/ES/DGA/B16-23R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-CIBERObn/CB06-03-1012
Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI/PID2019-104915RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-104915RB-I00
Tipo y forma: Article (Published version)
Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)
Área (Departamento): Área Producción Animal (Dpto. Produc.Animal Cienc.Ali.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes.
Exportado de SIDERAL (2025-09-22-14:29:22)
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Idioma: Inglés
DOI: 10.1016/j.jnutbio.2023.109503
Año: 2024
Publicado en: Journal of Nutritional Biochemistry 124, 109503 [13 pp.] (2024), 109503
ISSN: 0955-2863
Factor impacto JCR: 4.9 (2024)
Categ. JCR: NUTRITION & DIETETICS rank: 18 / 112 = 0.161 (2024) - Q1 - T1
Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 72 / 319 = 0.226 (2024) - Q1 - T1
Factor impacto SCIMAGO: 1.28 - Biochemistry (Q1) - Endocrinology, Diabetes and Metabolism (Q1) - Nutrition and Dietetics (Q1) - Clinical Biochemistry (Q1) - Molecular Biology (Q2)
Financiación: info:eu-repo/grantAgreement/ES/DGA/B16-23R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII-CIBERObn/CB06-03-1012
Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI/PID2019-104915RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-104915RB-I00
Tipo y forma: Article (Published version)
Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)
Área (Departamento): Área Producción Animal (Dpto. Produc.Animal Cienc.Ali.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. Exportado de SIDERAL (2025-09-22-14:29:22)
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Articles > Artículos por área > Bioquímica y Biología Molecular
Articles > Artículos por área > Ingeniería Química
Articles > Artículos por área > Producción Animal
Articles > Artículos por área > biologia_celular
Articles > Artículos por área > Fisiología
Record created 2024-01-16, last modified 2025-09-23