{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:00:44Z","timestamp":1792522844401,"version":"4.5.0"},"reference-count":66,"publisher":"American Physiological Society","issue":"7","funder":[{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de recherche en sant\u00e9 du Canada)","doi-asserted-by":"publisher","award":["5182"],"award-info":[{"award-number":["5182"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2016,4,1]]},"abstract":"<jats:p>Phosphatidylethanolamine N-methyltransferase (PEMT) is an important enzyme in hepatic phosphatidylcholine (PC) biosynthesis. Pemt<jats:sup>\u2212\/\u2212<\/jats:sup>mice are protected against high-fat diet (HFD)-induced obesity and insulin resistance; however, these mice develop nonalcoholic fatty liver disease (NAFLD). We hypothesized that peroxisomal proliferator-activated receptor-\u03b3 (PPAR\u03b3) activation by pioglitazone might stimulate adipocyte proliferation, thereby directing lipids from the liver toward white adipose tissue. Pioglitazone might also act directly on PPAR\u03b3 in the liver to improve NAFLD. Pemt<jats:sup>+\/+<\/jats:sup>and Pemt<jats:sup>\u2212\/\u2212<\/jats:sup>mice were fed a HFD with or without pioglitazone (20 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) for 10 wk. Pemt<jats:sup>\u2212\/\u2212<\/jats:sup>mice were protected from HFD-induced obesity but developed NAFLD. Treatment with pioglitazone caused an increase in body weight gain in Pemt<jats:sup>\u2212\/\u2212<\/jats:sup>mice that was mainly due to increased adiposity. Moreover, pioglitazone improved NAFLD in Pemt<jats:sup>\u2212\/\u2212<\/jats:sup>mice, as indicated by a 35% reduction in liver weight and a 57% decrease in plasma alanine transaminase levels. Livers from HFD-fed Pemt<jats:sup>\u2212\/\u2212<\/jats:sup>mice were steatotic, inflamed, and fibrotic. Hepatic steatosis was still evident in pioglitazone-treated Pemt<jats:sup>\u2212\/\u2212<\/jats:sup>mice; however, treatment with pioglitazone reduced hepatic fibrosis, as evidenced by reduced Sirius red staining and lowered mRNA levels of collagen type I\u03b1<jats:sub>1<\/jats:sub>( Col1a1), tissue inhibitor of metalloproteinases 1 ( Timp1), \u03b1-smooth muscle actin ( Acta2), and transforming growth factor-\u03b2 ( Tgf-\u03b2). Similarly, oxidative stress and inflammation were reduced in livers from Pemt<jats:sup>\u2212\/\u2212<\/jats:sup>mice upon treatment with pioglitazone. Together, these data show that activation of PPAR\u03b3 in HFD-fed Pemt<jats:sup>\u2212\/\u2212<\/jats:sup>mice improved liver function, while these mice were still protected against diet-induced obesity and insulin resistance.<\/jats:p>","DOI":"10.1152\/ajpgi.00243.2015","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T03:34:21Z","timestamp":1453433661000},"page":"G526-G538","source":"Crossref","is-referenced-by-count":45,"title":["Pioglitazone attenuates hepatic inflammation and fibrosis in phosphatidylethanolamine<i>N<\/i>-methyltransferase-deficient mice"],"prefix":"10.1152","volume":"310","author":[{"given":"Jelske N.","family":"van der Veen","sequence":"first","affiliation":[{"name":"Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, Alberta, Canada;"},{"name":"Department of Biochemistry, University of Alberta, Edmonton, Alberta, 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