{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T09:37:25Z","timestamp":1792229845700,"version":"4.4.0"},"reference-count":50,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIDDK","award":["R01DK124612"],"award-info":[{"award-number":["R01DK124612"]}]},{"name":"NIH\/NIDDK","award":["R01DK106540"],"award-info":[{"award-number":["R01DK106540"]}]},{"name":"NIH\/NIDDK","award":["P30 CA022453"],"award-info":[{"award-number":["P30 CA022453"]}]},{"name":"NIH\/NIDDK","award":["R21GM140352"],"award-info":[{"award-number":["R21GM140352"]}]},{"name":"NIH\/NIDDK","award":["R01DK124612"],"award-info":[{"award-number":["R01DK124612"]}]},{"name":"NIH\/NIDDK","award":["R01DK106540"],"award-info":[{"award-number":["R01DK106540"]}]},{"name":"NIH\/NIDDK","award":["P30 CA022453"],"award-info":[{"award-number":["P30 CA022453"]}]},{"name":"NIH\/NIDDK","award":["R21GM140352"],"award-info":[{"award-number":["R21GM140352"]}]},{"name":"NIH\/NCI","award":["R01DK124612"],"award-info":[{"award-number":["R01DK124612"]}]},{"name":"NIH\/NCI","award":["R01DK106540"],"award-info":[{"award-number":["R01DK106540"]}]},{"name":"NIH\/NCI","award":["P30 CA022453"],"award-info":[{"award-number":["P30 CA022453"]}]},{"name":"NIH\/NCI","award":["R21GM140352"],"award-info":[{"award-number":["R21GM140352"]}]},{"name":"NIH\/NIGMS","award":["R01DK124612"],"award-info":[{"award-number":["R01DK124612"]}]},{"name":"NIH\/NIGMS","award":["R01DK106540"],"award-info":[{"award-number":["R01DK106540"]}]},{"name":"NIH\/NIGMS","award":["P30 CA022453"],"award-info":[{"award-number":["P30 CA022453"]}]},{"name":"NIH\/NIGMS","award":["R21GM140352"],"award-info":[{"award-number":["R21GM140352"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pathogenesis roles of phospholipids (PLs) in nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This study investigated the role of PLs in the progression of NAFLD among obese individuals via studying the alterations in serum PL composition throughout the spectrum of disease progression and evaluating the effects of specific phosphatidylethanolamines (PEs) on FLD development in vitro. A total of 203 obese subjects, who were undergoing bariatric surgery, were included in this study. They were histologically classified into 80 controls (C) with normal liver histology, 93 patients with simple hepatic steatosis (SS), 16 with borderline nonalcoholic steatohepatitis (B-NASH) and 14 with progressive NASH (NASH). Serum PLs were profiled by automated electrospray ionization tandem mass spectrometry (ESI-MS\/MS). HepG2 (hepatoma cells) and LX2 (immortalized hepatic stellate cells or HSCs) were used to explore the roles of PL in NAFLD\/NASH development. Several PLs and their relative ratios were significantly associated with NAFLD progression, especially those involving PE. Incubation of HepG2 cells with two phosphatidylethanolamines (PEs), PE (34:1) and PE (36:2), resulted in significant inhibition of cell proliferation, reduction of mitochondrial mass and membrane potential, induction of lipid accumulation and mitochondrial ROS production. Meanwhile, treatment of LX2 cells with both PEs markedly increased cell activation and migration. These effects were associated with a significant change in the expression levels of genes involved in lipogenesis, lipid oxidation, autophagy, apoptosis, inflammation, and fibrosis. Thus, our study demonstrated that elevated level of PEs increases susceptibility to the disease progression of obesity associated NAFLD, likely through a causal cascade of impacts on the function of different liver cells.<\/jats:p>","DOI":"10.3390\/ijms24021034","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T05:29:48Z","timestamp":1672896588000},"page":"1034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Phosphatidylethanolamines Are Associated with Nonalcoholic Fatty Liver Disease (NAFLD) in Obese Adults and Induce Liver Cell Metabolic Perturbations and Hepatic Stellate Cell Activation"],"prefix":"10.3390","volume":"24","author":[{"given":"Samaa","family":"Shama","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA"},{"name":"Cell-Based Analysis Unit, Reference Laboratory, Egyptian Drug Authority, Cairo 12618, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyejeong","family":"Jang","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Core, Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA"},{"name":"Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaokun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-2935","authenticated-orcid":false,"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9746-5335","authenticated-orcid":false,"given":"Nancy Nabil","family":"Shahin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek Kamal","family":"Motawi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1120-073X","authenticated-orcid":false,"given":"Seongho","family":"Kim","sequence":"additional","affiliation":[{"name":"Biostatistics and Bioinformatics Core, Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA"},{"name":"Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samer","family":"Gawrieh","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA"},{"name":"Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA"},{"name":"Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.7861\/clinmedicine.18-3-245","article-title":"Non-alcoholic fatty liver disease","volume":"8","author":"Maurice","year":"2018","journal-title":"J. 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