{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:07:13Z","timestamp":1791256033454,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,1,13]],"date-time":"2014-01-13T00:00:00Z","timestamp":1389571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Artificial Organs"],"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Malnutrition is a common feature seen in chronic dialysis patients, and the survival rate of obese patients receiving such treatment is higher than that of lean patients. Irrespective of obesity or diabetes, dialysis patients commonly have insulin resistance, and the leading cause of death is cardiovascular (<jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content>) disease. It has been reported that the concentration of <jats:italic>p<\/jats:italic>\u2010cresol, a uremic toxin, is highly associated with <jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content> events. As uremic toxin levels are high in dialysis patients, they may be involved in the pathogenesis of insulin resistance and <jats:styled-content style=\"fixed-case\">CV<\/jats:styled-content> disease in this population. However, little is known so far. Thus, we focused on this uremic toxin to examine its effects on adipocytes and their precursors. 3<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>3\u2010<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>1 cells, a mouse preadipocyte cell line, were cultured until 90% confluency. The cells were then differentiated with 500\u2009\u03bcM 3\u2010isobutyl\u2010methylxanthine, 250\u2009nM dexamethasone, and 10\u2009\u03bcg\/mL insulin. Cell proliferation was evaluated by cell counting and bromodeoxyuridine (<jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>rd\u2010<jats:styled-content style=\"fixed-case\">U<\/jats:styled-content>) incorporation assay. Glucose uptake was estimated using radiolabeled 2\u2010deoxyglucose. The range of concentrations of <jats:italic>p<\/jats:italic>\u2010cresol used in the experiments was from 2 to 200\u2009\u03bcM. The investigation of cell proliferation by cell counting revealed that, compared with control, 3<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>3\u2010<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>1 cells treated with 100 and 200\u2009\u03bcM <jats:italic>p<\/jats:italic>\u2010cresol were significantly decreased in number at day 3 and day 7 of culture. The <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>rd\u2010<jats:styled-content style=\"fixed-case\">U<\/jats:styled-content> incorporation assay also demonstrated similar inhibitory effects on cell proliferation, suggesting that <jats:italic>p<\/jats:italic>\u2010cresol affected the normal cell cycle. Oil <jats:styled-content style=\"fixed-case\">R<\/jats:styled-content>ed <jats:styled-content style=\"fixed-case\">O<\/jats:styled-content> staining at day 7 showed that the number of mature adipocytes was decreased by treatment with 200\u2009\u03bcM <jats:italic>p<\/jats:italic>\u2010cresol. Consistent with that finding, the number of apoptotic cells at day 7 was increased by treatment with 100 and 200\u2009\u03bcM <jats:italic>p<\/jats:italic>\u2010cresol. Peroxisome proliferator\u2010activated receptor \u03b3 (<jats:styled-content style=\"fixed-case\">PPAR\u03b3<\/jats:styled-content>) <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression increased time\u2010dependently during the differentiation process of 3<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>3\u2010<jats:styled-content style=\"fixed-case\">L<\/jats:styled-content>1 cells. <jats:italic>p<\/jats:italic>\u2010Cresol dose\u2010dependently decreased differentiation\u2010induced <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression of <jats:styled-content style=\"fixed-case\">PPAR\u03b3<\/jats:styled-content>. Uptake of <jats:sup>3<\/jats:sup><jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>\u2010labeled 2\u2010deoxyglucose was markedly decreased by 200\u2009\u03bcM <jats:italic>p<\/jats:italic>\u2010cresol in the presence or in the absence of insulin, mainly because of the decreased number of mature adipocytes. High concentrations of <jats:italic>p<\/jats:italic>\u2010cresol disturbed the cell cycle, induced apoptosis, inhibited the differentiation of preadipocytes into mature adipocytes, and decreased glucose uptake at baseline and after insulin stimulation. These findings indicate that accumulated <jats:italic>p<\/jats:italic>\u2010cresol may induce reduction in adipose tissue, insulin resistance, and malnutrition, eventually leading to poor outcomes in chronic dialysis patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aor.12252","type":"journal-article","created":{"date-parts":[[2014,1,14]],"date-time":"2014-01-14T01:49:16Z","timestamp":1389664156000},"page":"566-571","source":"Crossref","is-referenced-by-count":20,"title":["Effects of Uremic Toxin <i>p<\/i>\u2010Cresol on Proliferation, Apoptosis, Differentiation, and Glucose Uptake in 3<scp>T<\/scp>3\u2010<scp>L<\/scp>1 Cells"],"prefix":"10.1111","volume":"38","author":[{"given":"Sayuri","family":"Tanaka","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Shimane University Faculty of Medicine  Izumo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shozo","family":"Yano","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Shimane University Faculty of Medicine  Izumo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah M.","family":"Sheikh","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Shimane University Faculty of Medicine  Izumo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Shimane University Faculty of Medicine  Izumo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshitsugu","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Shimane University Faculty of Medicine  Izumo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,1,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfq652"},{"key":"e_1_2_8_3_1","first-page":"264","article-title":"C\u2010reactive protein is a significant predictor of decrease in fat mass in hemodialysis patients","volume":"59","author":"Fujino Y","year":"2005","journal-title":"Biochem 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