{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:37Z","timestamp":1787028517511,"version":"build-2736575974"},"reference-count":70,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovations of the Republic of Serbia","award":["451-03-47\/2023-01\/200007"],"award-info":[{"award-number":["451-03-47\/2023-01\/200007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Age and sex influence serum cholesterol levels, but the underlying mechanisms remain unclear. To investigate further, we measured cholesterol, precursors (surrogate synthesis markers), degradation products (oxysterols and bile acid precursors) in serum, the liver, jejunum, and ileum, as well as serum plant sterols (intestinal absorption markers) in male and female Wistar rats (4 and 24 months old). The analysis of histomorphometric and oxidative stress parameters (superoxide dismutase, catalase, glutathione-related enzyme activities, lipid peroxide, and protein carbonyl concentrations) in the liver and jejunum offered further insights into the age- and sex-related differences. The hepatic gene expression analysis included AR, ER\u03b1, and sex-specific growth hormone-regulated (Cyp2c11 and Cyp2c12) and thyroid-responsive (Dio1, Tbg, and Spot 14) genes by qPCR. We observed age-related changes in both sexes, with greater prominence in females. Aged females had significantly higher serum cholesterol (p &lt; 0.05), jejunum cholesterol (p &lt; 0.05), and serum plant sterols (p &lt; 0.05). They exhibited poorer hepato-intestinal health compared with males, which was characterized by mild liver dysfunction (hydropic degeneration, increased serum ALT, p &lt; 0.05, and decreased activity of some antioxidant defense enzymes, p &lt; 0.05), mononuclear inflammation in the jejunal lamina propria, and age-related decreases in jejunal catalase and glutathione peroxidase activity (p &lt; 0.05). Aged females showed increased levels of 27-hydroxycholesterol (p &lt; 0.05) and upregulated ER\u03b1 gene expression (p &lt; 0.05) in the liver. Our study suggests that the more significant age-related increase in serum cholesterol in females is associated with poorer hepato-intestinal health and increased jejunal cholesterol absorption. The local increase in 27-hydroxycholesterol during aging might reduce the hepatoprotective effects of endogenous estrogen in the female liver.<\/jats:p>","DOI":"10.3390\/ijms241612624","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T10:11:22Z","timestamp":1691662282000},"page":"12624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Differences in Cholesterol Metabolism, Hepato-Intestinal Aging, and Hepatic Endocrine Milieu in Rats as Affected by the Sex and Age"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5496-0619","authenticated-orcid":false,"given":"Branka","family":"\u0160o\u0161i\u0107-Jurjevi\u0107","sequence":"first","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-8308","authenticated-orcid":false,"given":"Dieter","family":"L\u00fctjohann","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Trifunovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5651-7178","authenticated-orcid":false,"given":"Sla\u0111an","family":"Pavlovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4895-9985","authenticated-orcid":false,"given":"Slavica","family":"Borkovi\u0107 Miti\u0107","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1931-4475","authenticated-orcid":false,"given":"Ljubi\u0161a","family":"Jovanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Cytology, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Dr. Koste Todorovi\u0107a 26, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nata\u0161a","family":"Risti\u0107","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljiljana","family":"Marina","sequence":"additional","affiliation":[{"name":"National Centre for Infertility and Endocrinology of Gender, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Koste Todorovi\u0107a 6, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Ajd\u017eanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branko","family":"Filipovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Cytology, Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of Republic of Serbia, University of Belgrade, Bulevar Despota Stefana 142, 11060 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41392-022-01125-5","article-title":"Regulation of cholesterol homeostasis in health and diseases: From mechanisms to targeted therapeutics","volume":"7","author":"Duan","year":"2022","journal-title":"Signal Transduct. 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