{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T12:45:22Z","timestamp":1787748322069,"version":"build-2784847793"},"reference-count":47,"publisher":"Portland Press Ltd.","issue":"12","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,6,29]]},"abstract":"<jats:p>Apolipoprotein M (apoM) is a carrier and a modulator of sphingosine 1-phosphate (S1P), an important multifunctional bioactive lipid. Since peroxisome proliferator-activated receptor \u03b3 (PPAR\u03b3) is reportedly associated with the function and metabolism of S1P, we investigated the modulation of apoM\/S1P homeostasis by PPAR\u03b3. First, we investigated the modulation of apoM and S1P homeostasis by the overexpression or knockdown of PPAR\u03b3 in HepG2 cells and found that both the overexpression and the knockdown of PPAR\u03b3 decreased apoM expression and S1P synthesis. When we activated or suppressed the PPAR\u03b3 more mildly with pioglitazone or GW9662, we found that pioglitazone suppressed apoM expression and S1P synthesis, while GW9662 increased them. Next, we overexpressed PPAR\u03b3 in mouse liver through adenoviral gene transfer and observed that both the plasma and hepatic apoM levels and the plasma S1P levels decreased, while the hepatic S1P levels increased, in the presence of enhanced sphingosine kinase activity. Treatment with pioglitazone decreased both the plasma and hepatic apoM and S1P levels only in diet-induced obese mice. Moreover, the overexpression of apoM increased, while the knockdown of apoM suppressed PPAR\u03b3 activities in HepG2 cells. These results suggested that PPAR\u03b3 regulates the S1P levels by modulating apoM in a bell-shaped manner, with the greatest levels of apoM\/S1P observed when PPAR\u03b3 was mildly expressed and that hepatic apoM\/PPAR\u03b3 axis might maintain the homeostasis of S1P metabolism.<\/jats:p>","DOI":"10.1042\/bcj20180052","type":"journal-article","created":{"date-parts":[[2018,4,30]],"date-time":"2018-04-30T14:15:21Z","timestamp":1525097721000},"page":"2009-2024","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Regulation of the metabolism of apolipoprotein M and sphingosine 1-phosphate by hepatic PPAR\u03b3 activity"],"prefix":"10.1042","volume":"475","author":[{"given":"Makoto","family":"Kurano","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Iso-O","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masumi","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Medicine IV, Mizonokuchi Hospital, Teikyo University School of Medicine, Kawasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhisa","family":"Tsukamoto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Yatomi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,6,21]]},"reference":[{"key":"2021112216532003000_BCJ-2018-0052C1","doi-asserted-by":"publisher","first-page":"575","DOI":"10.2174\/138161206775474404","article-title":"Sphingosine 1-phosphate in vascular biology: possible therapeutic strategies to control vascular diseases","volume":"12","author":"Yatomi","year":"2006","journal-title":"Curr. 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