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Sterol regulatory element\u2010binding protein isoform 2 drives the intracellular cholesterol pathway in many tissues, including the testicles. Its abnormal regulation could be the mainly responsible for the failure of suppressing cholesterol synthesis in a cholesterol\u2010enriched environment, ultimately leading to testicular and seminal alterations. However, extra\u2010virgin olive oil consumption has beneficial properties that promote lowering of cholesterol levels, including the recovery of seminal parameters altered under a high\u2010fat diet.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n Our goal was to investigate the effects of high\u2010fat diet supplementation with extra\u2010virgin olive oil at the molecular level on rabbit testes, by analyzing sterol regulatory element\u2010binding protein isoform 2 protein and its corresponding downstream effectors.<\/jats:p>\n <\/jats:sec>\n \n Materials and methods<\/jats:title>\n During 12\u00a0months, male rabbits were fed a control diet, high\u2010fat diet, or 6\u2010month high\u2010fat diet followed by 6\u2010month high\u2010fat diet plus extra\u2010virgin olive oil. Serum lipids, testosterone levels, bodyweight, and seminal parameters were tested. The mRNA and protein levels of sterol regulatory element\u2010binding protein isoform 2, 3\u2010hydroxy\u20103\u2010methyl\u2010glutaryl\u2010coenzyme A reductase, and low\u2010density lipoprotein receptor were determined by semi\u2010quantitative polymerase chain reaction and Western blotting techniques. The expression pattern of sterol regulatory element\u2010binding protein isoform 2 protein in the rabbit testicles was studied by indirect immunofluorescence. In addition, testicular cholesterol was detected and quantified by filipin staining and gas chromatography.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The data showed that the addition of extra\u2010virgin olive oil to high\u2010fat diet reduced testicular cholesterol levels and recovered the expression of sterol regulatory element\u2010binding protein isoform 2, 3\u2010hydroxy\u20103\u2010methyl\u2010glutaryl\u2010coenzyme A reductase, and low\u2010density lipoprotein receptor initially altered by the high\u2010fat diet.<\/jats:p>\n <\/jats:sec>\n \n Discussion and conclusions<\/jats:title>\n The combination of high\u2010fat diet with extra\u2010virgin olive oil encourages testicular recovery by modifying the expression of the enzymes related to intracellular cholesterol management.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/andr.13398","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T10:17:37Z","timestamp":1674641857000},"page":"1203-1217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Extra\u2010virgin olive oil ameliorates high\u2010fat diet\u2010induced seminal and testicular disorders by modulating the cholesterol pathway"],"prefix":"10.1111","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6540-3324","authenticated-orcid":false,"given":"Abi Karenina","family":"Funes","sequence":"first","affiliation":[{"name":"Laboratorio de Biolog\u00eda Molecular del Metabolismo & Nutrici\u00f3n (MeNu). 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