000165736 001__ 165736
000165736 005__ 20260113234335.0
000165736 0247_ $$2doi$$a10.3390/ijms262411994
000165736 0248_ $$2sideral$$a147330
000165736 037__ $$aART-2025-147330
000165736 041__ $$aeng
000165736 100__ $$0(orcid)0000-0002-8100-5596$$aMartínez-Beamonte, Roberto$$uUniversidad de Zaragoza
000165736 245__ $$aThe Disruption of Cyp7b1 Controls IGFBP2 and Prediabetes Exerted Through Different Hydroxycholesterol Metabolites
000165736 260__ $$c2025
000165736 5060_ $$aAccess copy available to the general public$$fUnrestricted
000165736 5203_ $$aCytochrome P450, family 7, subfamily b, polypeptide 1 (CYP7B1) is a widely expressed enzyme involved in the hydroxylation of sterols. Generated by transposon technology in zygotes, male rats lacking Cyp7b1 expression in homozygosis showed an absence of Cyp7b1 mRNA expression in the liver, small intestine, adipose tissue, and muscle. Elevated levels of 25-hydroxycholesterol were found in the liver of mutant rats. After overnight fasting, plasma triglyceride (TG) levels were increased in the homozygous rats. In agreement with this, increased hepatic secretion of very-low-density lipoprotein-TG (VLDL) in fasting rats treated with tyloxapol and decreased low-density receptor protein (LDLr) on the hepatocyte plasma membranes were observed. The decrease in LDLr was not due to decreased mRNA expression but to increased expressions of its proteases (Psck9 and Mylip). RNA sequencing identified Fasn, Igfbp2, and Pcsk9 as targets of the Cyp7b1 absence. However, the hepatic protein contents of IGFBP2 were increased in Cyp7b1-deficient rats, accompanied by a normal glucose tolerance test. HepG2 cells lacking CYP7B1 showed increased expressions of FASN and IGFBP2. These results suggest a role of CYP7B1 in the control of hepatic IGFBP2 and VLDL-TG secretion as a prediabetes sign exerted through 25-hydroxycholesterol and transcriptional or translational mechanisms depending on the species.
000165736 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B16-23R$$9info:eu-repo/grantAgreement/ES/DGA/B45-23R$$9info:eu-repo/grantAgreement/ES/DGA/PI025-08$$9info:eu-repo/grantAgreement/ES/DGA/T53-23R$$9info:eu-repo/grantAgreement/ES/ISCIII/CB06-03-1012$$9info:eu-repo/grantAgreement/ES/MCINN/PID2022-136414OB-I00$$9info:eu-repo/grantAgreement/ES/MICIU/PRTR-C17.I1
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000165736 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000165736 700__ $$0(orcid)0000-0001-6627-298X$$aGuillén, Natalia$$uUniversidad de Zaragoza
000165736 700__ $$0(orcid)0000-0002-9023-741X$$aSánchez-Marco, Javier
000165736 700__ $$0(orcid)0000-0002-4665-9674$$aHerrera-Marcos, Luis V.$$uUniversidad de Zaragoza
000165736 700__ $$0(orcid)0000-0002-5841-0462$$aSurra, Joaquín C.
000165736 700__ $$0(orcid)0000-0002-0108-1004$$aNavarro, María A.$$uUniversidad de Zaragoza
000165736 700__ $$0(orcid)0000-0002-8442-8041$$aBarranquero, Cristina
000165736 700__ $$0(orcid)0000-0002-5152-1071$$aArnal, Carmen
000165736 700__ $$0(orcid)0000-0002-7213-7095$$aPuente, Juan J.
000165736 700__ $$0(orcid)0000-0002-3595-7668$$aRodríguez-Yoldi, Mª Jesús$$uUniversidad de Zaragoza
000165736 700__ $$0(orcid)0000-0001-8830-6554$$aMendiara, Isabel
000165736 700__ $$0(orcid)0000-0001-8893-0963$$aDomeño, Celia$$uUniversidad de Zaragoza
000165736 700__ $$0(orcid)0000-0003-2685-5739$$aNerín, Cristina$$uUniversidad de Zaragoza
000165736 700__ $$aGeurts, Aron M.
000165736 700__ $$0(orcid)0000-0002-8251-8457$$aOsada, Jesús$$uUniversidad de Zaragoza
000165736 700__ $$0(orcid)0000-0003-3963-0846$$aLaclaustra, Martín$$uUniversidad de Zaragoza
000165736 7102_ $$12009$$2750$$aUniversidad de Zaragoza$$bDpto. Química Analítica$$cÁrea Química Analítica
000165736 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000165736 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000165736 7102_ $$11012$$2315$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Farmacología
000165736 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000165736 7102_ $$11002$$2807$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Toxicología
000165736 773__ $$g26, 24 (2025), 11994 [19 pp.]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000165736 8564_ $$s6126702$$uhttps://zaguan.unizar.es/record/165736/files/texto_completo.pdf$$yVersión publicada
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