{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:25:55Z","timestamp":1786951555614,"version":"build-2736575974"},"reference-count":61,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alternate\u2010day fasting (ADF) may exert age\u2010related anti\u2010inflammatory effects by modulating key metabolic and immune pathways. This study aimed to investigate the sex\u2010specific effects of ADF on inflammation in middle\u2010aged male and female rats and focused on the Toll\u2010like receptor 4 (TLR4) and leptin signaling pathways. A total of 32 rats (16 males, 16 females; 14 months old) were assigned to four groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20098): ad libitum\u2010fed and ADF groups for each sex. The ADF protocol consisted of 24\u2010h fasting every other day for 2 months. Serum and hypothalamic samples were analyzed via ELISA to measure triglyceride, total cholesterol, tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), interleukin\u20106 (IL\u20106), suppressor of cytokine signaling 3 (SOCS3), leptin, and ObRb levels. TLR4 gene expression in the brain and liver was assessed via qRT\u2013PCR. Two months of ADF significantly reduced body weight and retroperitoneal fat mass compared with those of the control groups (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Cumulative food intake and fasting glucose levels decreased in both sexes following ADF (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001), and serum triglyceride, total cholesterol, TNF\u2010\u03b1, and IL\u20106 levels (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) were significantly reduced. Hypothalamic SOCS3 and leptin levels decreased, whereas ObRb expression increased (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Additionally, TLR4 gene expression was significantly downregulated in both tissues (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). These findings suggest that ADF is associated with reduced age\u2010related inflammation and alterations in the TLR4 and leptin signaling pathways. The observed downregulation of SOCS3 and upregulation of ObRb indicate enhanced leptin sensitivity, highlighting ADF as a promising strategy to counteract sex\u2010specific aging\u2010related inflammation and leptin resistance.\n                  <\/jats:p>","DOI":"10.1002\/jbt.71051","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:44:12Z","timestamp":1785408252000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex\u2010Specific Anti\u2010Inflammatory Effects of Alternate Day Fasting via TLR4 and Leptin Signaling in Middle\u2010Aged Rats"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8037-099X","authenticated-orcid":false,"given":"Ozgen","family":"Kilic\u2010Erkek","sequence":"first","affiliation":[{"name":"Department of Physiology Pamukkale University, Faculty of Medicine Denizli Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9924-5176","authenticated-orcid":false,"given":"Gulsah","family":"Gundogdu","sequence":"additional","affiliation":[{"name":"Department of Physiology Pamukkale University, Faculty of Medicine Denizli Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8346-2510","authenticated-orcid":false,"given":"Abdullah","family":"Coguplugil","sequence":"additional","affiliation":[{"name":"Pamukkale University, Experimental Surgery Application And Research Center Denizli Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4936-5954","authenticated-orcid":false,"given":"Yavuz","family":"Dodurga","sequence":"additional","affiliation":[{"name":"Department of Medical Biology Pamukkale University, Faculty of Medicine Denizli Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0059-4"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2021.01.006"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101323"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-3681-2_2"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2022.101812"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.2144\/Oct0208"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12979-023-00383-3"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20030769"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/212563"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19905"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573399816666191230111838"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2006.09.007"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2014.06.001"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-48382-5_16"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13937"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2020.11.008"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2016.10.005"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101161"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2021.111244"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000357765"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.7136.1"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17114138"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/962012"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-015-9578-8"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1413965111"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuv041"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2017.02.032"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.994827"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-789X.2011.00873.x"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12041029"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12291-024-01220-0"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2023.112198"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1905136"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9076485"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2009.05.004"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12221"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2007.09.002"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2010.08.007"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.3109\/13813455.2011.577435"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0543"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2016.01.015"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.2152\/jmi.71.246"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01800"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2019.114871"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041742"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.4161\/jkst.23878"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42000-018-0078-5"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.02.004"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2008.08.005"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80062-3"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2010.08.002"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2012.09.005"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22065"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071816-064634"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.12.021"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1017\/S002966511200078X"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-1207"},{"key":"e_1_2_14_59_1","first-page":"265","article-title":"Adipokines and the Endocrine Role of Adipose Tissues","volume":"235","author":"Giralt M.","year":"2016","journal-title":"Metabolic control"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1200"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2015.10.019"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2019.02.020"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.71051","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.71051","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.71051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T07:01:42Z","timestamp":1786950102000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.71051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,30]]},"references-count":61,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/jbt.71051"],"URL":"https:\/\/doi.org\/10.1002\/jbt.71051","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,30]]},"assertion":[{"value":"2025-07-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71051"}}