{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:07:48Z","timestamp":1790208468681,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in most parts of the world. Although there is no first-line drug approved for the treatment of NAFLD, polyene phosphatidylcholine (PPC) is used by clinicians to treat NAFLD patients. This study aimed to evaluate the efficacy of PPC on a mice model of NAFLD, and to study the PPC\u2019s mechanism of action. The mice were fed a choline-deficient, L-amino acid-defined (CDAA) diet to induce NAFLD and were subsequently treated with PPC. The treatment effects were evaluated by the liver index, histopathological examination, and routine blood chemistry analyses. Lipidomics and metabolomics analyses of 54 samples were carried out using ultraperformance liquid chromatography (UPLC) coupled to a mass spectrometer to select for changes in metabolites associated with CDAA diet-induced NAFLD and the effects of PPC treatment. The intestinal flora of mice were extracted for gene sequencing to find differences before and after the induction of NAFLD and PPC treatment. PPC significantly improved the CDAA diet-induced NAFLD condition in mice. A total of 19 metabolites including 5 polar metabolites and 14 lipids showed marked changes. In addition, significant differences in the abundance of Lactobacillus were associated with NAFLD. We inferred that the protective therapeutic effect of PPC on the liver was related to the supplement of phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin (PC, LPC, and SM, resectively) and acylcarnitine metabolism. This study developed a methodology for exploring the pathogenesis of NAFLD and can be extended to other therapeutic agents for treating NAFLD.<\/jats:p>","DOI":"10.3390\/ijms24021502","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T05:03:03Z","timestamp":1673499783000},"page":"1502","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Changes in Lipidomics, Metabolomics, and the Gut Microbiota in CDAA-Induced NAFLD Mice after Polyene Phosphatidylcholine Treatment"],"prefix":"10.3390","volume":"24","author":[{"given":"Jiayuan","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Zang","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxiao","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yicong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9504-891X","authenticated-orcid":false,"given":"Mingming","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.4254\/wjh.v7.i13.1788","article-title":"Non-alcohol fatty liver disease in Asia: Prevention and planning","volume":"7","author":"Ashtari","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/aje\/kws448","article-title":"Prevalence of nonalcoholic fatty liver disease in the United States: The Third National Health and Nutrition Examination Survey, 1988\u20131994","volume":"178","author":"Lazo","year":"2013","journal-title":"Am. J. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.cgh.2014.04.014","article-title":"Fibrosis progression in nonalcoholic fatty liver vs. nonalcoholic steatohepatitis: A systematic review and meta-analysis of paired-biopsy studies","volume":"13","author":"Singh","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tarantino, G., Citro, V., and Capone, D. (2019). Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010015"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrgastro.2016.85","article-title":"The role of the gut microbiota in NAFLD","volume":"13","author":"Leung","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"154925","DOI":"10.1016\/j.metabol.2021.154925","article-title":"Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease","volume":"126","author":"Negi","year":"2022","journal-title":"Metabolism"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/j.jhep.2009.01.025","article-title":"Polyenephosphatidylcholine prevents alcoholic liver disease in PPARalpha-null mice through attenuation of increases in oxidative stress","volume":"50","author":"Okiyama","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/S0022-3468(03)00393-2","article-title":"Protective effect of polyunsaturated phosphatidylcholine on liver damage induced by biliary obstruction in rats","volume":"38","author":"Karaman","year":"2003","journal-title":"J. Pediatr. Surg."},{"key":"ref_10","first-page":"2683","article-title":"Morphological and functional characterization of non-alcoholic fatty liver disease induced by a methionine-choline-deficient diet in C57BL\/6 mice","volume":"6","author":"Hiroko","year":"2013","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jhep.2003.09.020","article-title":"The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance","volume":"40","author":"Rinella","year":"2004","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1038\/s41598-017-03675-z","article-title":"Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis","volume":"7","author":"Cabrera","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1007\/s10620-018-5395-7","article-title":"Disease Progression and Pharmacological Intervention in a Nutrient-Deficient Rat Model of Nonalcoholic Steatohepatitis","volume":"64","author":"Tolbol","year":"2019","journal-title":"Dig. Dis. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1080\/10406638.2019.1689404","article-title":"Zn (BDC)-(MOF): Introduction of a New Catalyst for the Synthesis Pyrimido[4,5-d]Pyrimidine Derivatives under Ultrasound Irradiation in the Absence of Solvent","volume":"41","author":"Shirini","year":"2021","journal-title":"Polycycl. Aromat. Compd."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"23916","DOI":"10.1074\/jbc.M312676200","article-title":"A choline-deficient diet in mice inhibits neither the CDP-choline pathway for phosphatidylcholine synthesis in hepatocytes nor apolipoprotein B secretion","volume":"279","author":"Kulinski","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1872-034X.2010.00769.x","article-title":"Pitavastatin inhibits hepatic steatosis and fibrosis in non-alcoholic steatohepatitis model rats","volume":"41","author":"Miyaki","year":"2011","journal-title":"Hepatol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1801585","DOI":"10.1002\/advs.201801585","article-title":"Insights into the Epidemiology, Pathogenesis, and Therapeutics of Nonalcoholic Fatty Liver Diseases","volume":"6","author":"Yu","year":"2019","journal-title":"Adv. Sci."},{"key":"ref_18","first-page":"20","article-title":"Pathogenesis and treatment of alcoholic liver disease: Progress over the last 50 years","volume":"5","author":"Lieber","year":"2005","journal-title":"Rocz. Akad. Med. Bialymst."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1097\/01.ALC.0000171896.37022.F7","article-title":"Alcoholic liver disease: From pathophysiology to therapy","volume":"29","author":"Seitz","year":"2005","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1194\/jlr.R700019-JLR200","article-title":"Phosphatidylcholine and choline homeostasis","volume":"49","author":"Li","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"165720","DOI":"10.1016\/j.bbadis.2020.165720","article-title":"Metabolic interactions between peroxisomes and mitochondria with a special focus on acylcarnitine metabolism","volume":"1866","author":"Houten","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Savic, D., Hodson, L., Neubauer, S., and Pavlides, M. (2020). The Importance of the Fatty Acid Transporter L-Carnitine in Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients, 12.","DOI":"10.3390\/nu12082178"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.dsx.2018.08.035","article-title":"Comparative study to evaluate the effect of l-carnitine plus glimepiride versus glimepiride alone on insulin resistance in type 2 diabetic patients","volume":"13","author":"Elbedewy","year":"2019","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"333","DOI":"10.17219\/acem\/61609","article-title":"L-carnitine treatment of insulin resistance: A systematic review and meta-analysis","volume":"26","author":"Xu","year":"2017","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1093\/alcalc\/agh142","article-title":"DLPC attenuates alcohol-induced cytotoxicity in HepG2 cells expressing CYP2E1","volume":"40","author":"Xu","year":"2005","journal-title":"Alcohol Alcohol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0009-9120(01)00218-1","article-title":"Signaling for ethanol-induced apoptosis and repair in vitro","volume":"34","author":"Katz","year":"2001","journal-title":"Clin. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"287","DOI":"10.37349\/emed.2020.00019","article-title":"Nonalcoholic fatty liver disease and type 2 diabetes: Pathophysiological mechanisms shared between the two faces of the same coin","volume":"1","author":"Acierno","year":"2020","journal-title":"Explor. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"468","DOI":"10.2337\/dc13-1359","article-title":"Lower Fasting Muscle Mitochondrial Activity Relates to Hepatic Steatosis in Humans","volume":"37","author":"Szendroedi","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1002\/hep.1840380426","article-title":"Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis","volume":"38","author":"Rubio","year":"2003","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3945\/ajcn.110.010132","article-title":"Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans","volume":"94","author":"Jumpertz","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1038\/nature05414","article-title":"An obesity-associated gut microbiome with increased capacity for energy harvest","volume":"444","author":"Turnbaugh","year":"2006","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"455","DOI":"10.4161\/gmic.21216","article-title":"Is bile acid a determinant of the gut microbiota on a high-fat diet?","volume":"3","author":"Yokota","year":"2012","journal-title":"Gut Microbes"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6680","DOI":"10.1002\/jsfa.9945","article-title":"Probiotic potential comparison of Lactobacillus strains isolated from Iranian traditional food products and human feces with standard probiotic strains","volume":"99","author":"Joghataei","year":"2019","journal-title":"J. Sci. Food Agric."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"103760","DOI":"10.1016\/j.micpath.2019.103760","article-title":"Probiotic potential of Lactobacillus on the intestinal microflora against Escherichia coli induced mice model through high-throughput sequencing","volume":"137","author":"Wang","year":"2019","journal-title":"Microb. Pathog."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"fnz254","DOI":"10.1093\/femsle\/fnz254","article-title":"Lactobacillus reuteri A9 and Lactobacillus mucosae A13 isolated from Chinese superlongevity people modulate lipid metabolism in a hypercholesterolemia rat model","volume":"366","author":"Jiang","year":"2019","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/S1665-2681(19)31364-X","article-title":"Treatment of nonalcoholic steatohepatitis with probiotics. A proof-of-concept study","volume":"12","author":"Vincent","year":"2013","journal-title":"Ann. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jnutbio.2014.10.016","article-title":"Enhanced AMPK phosphorylation contributes to the beneficial effects of Lactobacillus rhamnosus GG supernatant on chronic-alcohol-induced fatty liver disease","volume":"26","author":"Zhang","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/s41587-020-0531-2","article-title":"A lipidome atlas in MS-DIAL 4","volume":"38","author":"Tsugawa","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1194\/jlr.RA119000346","article-title":"Dietary inulin decreases circulating ceramides by suppressing neutral sphingomyelinase expression and activity in mice","volume":"61","author":"Deng","year":"2020","journal-title":"J. Lipid Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nmeth.3393","article-title":"MS-DIAL: Data-independent MS\/MS deconvolution for comprehensive metabolome analysis","volume":"12","author":"Tsugawa","year":"2015","journal-title":"Nat. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1502\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:04:12Z","timestamp":1760119452000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,12]]},"references-count":40,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24021502"],"URL":"https:\/\/doi.org\/10.3390\/ijms24021502","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,12]]}}}