{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:43:02Z","timestamp":1787168582648,"version":"build-2736575974"},"reference-count":87,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T00:00:00Z","timestamp":1648512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01CA136493"],"award-info":[{"award-number":["R01CA136493"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54TR001629"],"award-info":[{"award-number":["U54TR001629"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31CA165665"],"award-info":[{"award-number":["F31CA165665"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Obesity, oxidative stress, and inflammation are risk factors for hepatocellular carcinoma (HCC). We examined, in mice, the effects of Kr\u00fcppel-like factor 9 (KLF9) knockout on: adiposity, hepatic and systemic oxidative stress, and hepatic expression of pro-inflammatory and NOX\/DUOX family genes, in a high-fat diet (HFD) context. Male and female Klf9+\/+ (wild type, WT) and Klf9\u2212\/\u2212 (knockout, KO) mice were fed HFD (beginning at age 35 days) for 12 weeks, after which liver and adipose tissues were obtained, and serum adiponectin and leptin levels, liver fat content, and markers of oxidative stress evaluated. Klf9\u2212\/\u2212 mice of either sex did not exhibit significant alterations in weight gain, adipocyte size, adipokine levels, or liver fat content when compared to WT counterparts. However, Klf9\u2212\/\u2212 mice of both sexes had increased liver weight\/size (hepatomegaly). This was accompanied by increased hepatic oxidative stress as indicated by decreased GSH\/GSSG ratio and increased homocysteine, 3-nitrotyrosine, 3-chlorotyrosine, and 4HNE content. Decreased GSH to GSSG ratio and a trend toward increased homocysteine levels were observed in the corresponding Klf9\u2212\/\u2212 mouse serum. Gene expression analysis showed a heightened pro-inflammatory state in livers from Klf9\u2212\/\u2212 mice. KLF9 suppresses hepatic oxidative stress and inflammation, thus identifying potential mechanisms for KLF9 suppression of HCC and perhaps cancers of other tissues.<\/jats:p>","DOI":"10.3390\/cancers14071737","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:40:14Z","timestamp":1648590014000},"page":"1737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Kr\u00fcppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet"],"prefix":"10.3390","volume":"14","author":[{"given":"Adam R.","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9200-9587","authenticated-orcid":false,"given":"Iad","family":"Alhallak","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalia C. M.","family":"Simmen","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stepan B.","family":"Melnyk","sequence":"additional","affiliation":[{"name":"Arkansas Children\u2019s Research Institute, Little Rock, AR 72202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa E.","family":"Heard-Lipsmeyer","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Theresa E.","family":"Montales","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Habenicht","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trang T.","family":"Van","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A.","family":"Simmen","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"},{"name":"The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"ref_1","first-page":"17","article-title":"Globesity: The root causes of the obesity epidemic in the USA and now worldwide","volume":"12","author":"Lifshitz","year":"2014","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1097\/CEJ.0b013e328348fc21","article-title":"The maternal womb: A novel target for cancer prevention in the era of the obesity pandemic?","volume":"20","author":"Simmen","year":"2011","journal-title":"Eur. J. 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