{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:08:09Z","timestamp":1791526089897,"version":"4.3.4"},"reference-count":69,"publisher":"American Physiological Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:p>Hepatic inflammation and fibrosis are key elements in the pathogenesis of nonalcoholic steatohepatitis (NASH), a progressive liver disease initiated by excess hepatic lipid accumulation. Lipid droplet protein Perilipin 2 (Plin2) alleviates dietary-induced hepatic steatosis when globally ablated; however, its role in the progression of NASH remains unknown. To investigate this further, we challenged Plin2 liver-specific knockout mice (designated L-KO) and their respective wild-type (WT) controls with a methionine-choline-deficient (MCD) diet for 15 days to induce a NASH phenotype of increased hepatic triglyceride levels through impaired phosphatidylcholine (PC) synthesis and very-low-density lipoprotein (VLDL) secretion. Results on liver weights, body weights, fat tissue mass, and histology in WT and L-KO mice fed the MCD diet revealed signs of hepatic steatosis, fibrosis, and inflammation; however, these effects were blunted in L-KO mice. In addition, levels of PC and VLDL were unchanged, and hepatic steatosis was reduced in L-KO mice fed the MCD diet, due in part to an increase in remodeling of PE to PC via the enzyme phosphatidylethanolamine N-methyltransferase (PEMT). These mice also exhibited decreased hepatic expression of proinflammatory markers cyclooxygenase 2, IL-6, TNF-\u03b1, IL-1\u03b2, and reduced expression of endoplasmic reticulum (ER) stress proteins C\/EBP homologous protein and cleaved caspase-1. Taken together, these results suggest that Plin2 liver-specific ablation alleviates diet-induced hepatic steatosis and inflammation via a PEMT-mediated mechanism that involves compensatory changes in proteins involved in phospholipid remodeling, inflammation, and ER stress that work to alleviate diet-induced NASH. Overall, these findings support a role for Plin2 as a target for NASH therapy.<\/jats:p>","DOI":"10.1152\/ajpgi.00436.2015","type":"journal-article","created":{"date-parts":[[2016,3,11]],"date-time":"2016-03-11T22:38:30Z","timestamp":1457735910000},"page":"G726-G738","source":"Crossref","is-referenced-by-count":144,"title":["Liver-specific loss of Perilipin 2 alleviates diet-induced hepatic steatosis, inflammation, and fibrosis"],"prefix":"10.1152","volume":"310","author":[{"given":"Charles P.","family":"Najt","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subramanian","family":"Senthivinayagam","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad B.","family":"Aljazi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Fader","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra D.","family":"Olenic","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julienne R. 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