{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:07:05Z","timestamp":1791515225334,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T00:00:00Z","timestamp":1695168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Research Funds for the Central Universities","award":["E2E43202X2"],"award-info":[{"award-number":["E2E43202X2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is the primary chronic liver disease worldwide, mainly manifested by hepatic steatosis. Hepatic lipids may be derived from dietary intake, plasma free fatty acid (FFA) uptake, or hepatic de novo lipogenesis (DNL). Currently, cellular and animal models of hepatocellular steatosis are widely used to study the pathogenesis of NAFLD and to investigate therapeutic agents. However, whether there are differences between the in vivo and in vitro models of the mechanisms that cause lipid accumulation has not been reported. We used OA\/PA-induced NCTC 1469 cells and high-fat-diet-fed C57BL\/6J mice to simulate a hepatocyte steatosis model of NAFLD and to detect indicators related to FFA uptake and DNL. In addition, when serological indicators were analysed in the mouse model, it was found that serum FASN levels decreased. The results revealed that, in the cellular model, indicators related to DNL were decreased, FASN enzyme activity was unchanged, and indicators related to FFA uptake were increased, including the high expression of CD36; while, in the animal model, indicators related to both FFA uptake and de novo synthesis were increased, including the high expression of CD36 and the increased protein levels of FASN with enhanced enzyme activity. In addition, after an analysis of the serological indicators in the mouse model, it was found that the serum levels of FASN were reduced. In conclusion, the OA\/PA-induced cellular model can be used to study the mechanism of FFA uptake, whereas the high-fat-diet-induced mouse model can be used to study the mechanism of FFA uptake and DNL. Combined treatment with CD36 and FASN may be more effective against NAFLD. FASN in the serum can be used as one of the indicators for the clinical diagnosis of NAFLD.<\/jats:p>","DOI":"10.3390\/molecules28186714","type":"journal-article","created":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T22:38:45Z","timestamp":1695249525000},"page":"6714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["The Different Mechanisms of Lipid Accumulation in Hepatocytes Induced by Oleic Acid\/Palmitic Acid and High-Fat Diet"],"prefix":"10.3390","volume":"28","author":[{"given":"Miao","family":"Zhang","sequence":"first","affiliation":[{"name":"Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Bai","sequence":"additional","affiliation":[{"name":"Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Du","sequence":"additional","affiliation":[{"name":"Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaojiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keting","family":"Dong","sequence":"additional","affiliation":[{"name":"Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyue","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Nursing, Capital Medical University, Beijing 100069, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Savaid Medical School, University of Chinese Academy of Sciences, Beijing 101400, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cmet.2017.08.002","article-title":"Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases","volume":"27","author":"Samuel","year":"2018","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ijbiomac.2020.04.167","article-title":"Study on structure characterization of pectin from the steamed ginseng and the inhibition activity of lipid accumulation in oleic acid-induced HepG2 cells","volume":"159","author":"Jiao","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"818159","DOI":"10.3389\/fphar.2022.818159","article-title":"Protective Effect of Isoorientin on Oleic Acid-Induced Oxidative Damage and Steatosis in Rat Liver Cells","volume":"13","author":"Luo","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1124\/jpet.120.000162","article-title":"Apigenin Ameliorates Insulin Resistance and Lipid Accumulation by Endoplasmic Reticulum Stress and SREBP-1c\/SREBP-2 Pathway in Palmitate-Induced HepG2 Cells and High-Fat Diet-Fed Mice","volume":"377","author":"Wu","year":"2021","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_6","first-page":"4557532","article-title":"Cimifugin Ameliorates Lipotoxicity-Induced Hepatocyte Damage and Steatosis through TLR4\/p38 MAPK- and SIRT1-Involved Pathways","volume":"2022","author":"Yang","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.apsb.2019.02.006","article-title":"Silibinin ameliorates hepatic lipid accumulation and oxidative stress in mice with non-alcoholic steatohepatitis by regulating CFLAR-JNK pathway","volume":"9","author":"Liu","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mun, J., Kim, S., Yoon, H.G., You, Y., Kim, O.K., Choi, K.C., Lee, Y.H., Lee, J., Park, J., and Jun, W. (2019). Water Extract of Curcuma longa L. Ameliorates Non-Alcoholic Fatty Liver Disease. Nutrients, 11.","DOI":"10.3390\/nu11102536"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1016\/j.molcel.2022.01.021","article-title":"Amelioration of hepatic steatosis by dietary essential amino acid-induced ubiquitination","volume":"82","author":"Zhang","year":"2022","journal-title":"Mol. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e145889","DOI":"10.1172\/JCI145889","article-title":"Targeting hepatic kisspeptin receptor ameliorates nonalcoholic fatty liver disease in a mouse model","volume":"132","author":"Guzman","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.jhep.2020.04.011","article-title":"Animal models for liver disease-A practical approach for translational research","volume":"73","author":"Nevzorova","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.1038\/s41467-020-18565-8","article-title":"CD36 facilitates fatty acid uptake by dynamic palmitoylation-regulated endocytosis","volume":"11","author":"Hao","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.cmet.2020.05.018","article-title":"Local Mitochondrial ATP Production Regulates Endothelial Fatty Acid Uptake and Transport","volume":"32","author":"Ibrahim","year":"2020","journal-title":"Cell Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e20221316","DOI":"10.1084\/jem.20221316","article-title":"Repurposing a tricyclic antidepressant in tumor and metabolism disease treatment through fatty acid uptake inhibition","volume":"220","author":"Chu","year":"2023","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.trecan.2020.03.001","article-title":"Drilling for Oil: Tumor-Surrounding Adipocytes Fueling Cancer","volume":"6","author":"Attane","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrd2589","article-title":"Fatty acid-binding proteins: Role in metabolic diseases and potential as drug targets","volume":"7","author":"Furuhashi","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/1479-7364-5-3-170","article-title":"The human fatty acid-binding protein family: Evolutionary divergences and functions","volume":"5","author":"Smathers","year":"2011","journal-title":"Hum. Genom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"30360","DOI":"10.1074\/jbc.271.48.30360","article-title":"Molecular cloning of cDNA encoding rat very long-chain acyl-CoA synthetase","volume":"271","author":"Uchiyama","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"105228","DOI":"10.1016\/j.phrs.2020.105228","article-title":"FATP2-targeted therapies-A role beyond fatty liver disease","volume":"161","author":"Qiu","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.mam.2012.07.010","article-title":"SLC27 fatty acid transport proteins","volume":"34","author":"Anderson","year":"2013","journal-title":"Mol. Aspects Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15547","DOI":"10.1074\/jbc.M113.473298","article-title":"Sulfo-N-succinimidyl oleate (SSO) inhibits fatty acid uptake and signaling for intracellular calcium via binding CD36 lysine 164: SSO also inhibits oxidized low density lipoprotein uptake by macrophages","volume":"288","author":"Kuda","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1210\/en.2015-1866","article-title":"Hepatocyte-Specific Disruption of CD36 Attenuates Fatty Liver and Improves Insulin Sensitivity in HFD-Fed Mice","volume":"157","author":"Wilson","year":"2016","journal-title":"Endocrinology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3951","DOI":"10.1021\/acs.analchem.0c04866","article-title":"CD36 as a Molecular Target of Functional DNA Aptamer NAFLD01 Selected against NAFLD Cells","volume":"93","author":"Pu","year":"2021","journal-title":"Anal. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/j.jhep.2018.01.035","article-title":"Prolactin improves hepatic steatosis via CD36 pathway","volume":"68","author":"Zhang","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41419-022-04812-x","article-title":"B-cell lymphoma 6 alleviates nonalcoholic fatty liver disease in mice through suppression of fatty acid transporter CD36","volume":"13","author":"Zhang","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.7150\/ijbs.54604","article-title":"Berberine alleviates lipid metabolism disorders via inhibition of mitochondrial complex I in gut and liver","volume":"17","author":"Yu","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.biopha.2018.05.135","article-title":"Curcumin regulates endogenous and exogenous metabolism via Nrf2-FXR-LXR pathway in NAFLD mice","volume":"105","author":"Yan","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Huang, X., Chen, W., Yan, C., Yang, R., Chen, Q., Xu, H., and Huang, Y. (2019). Gypenosides improve the intestinal microbiota of non-alcoholic fatty liver in mice and alleviate its progression. Biomed. Pharmacother., 118.","DOI":"10.1016\/j.biopha.2019.109258"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1172\/JCI23621","article-title":"Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease","volume":"115","author":"Donnelly","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13080","DOI":"10.1021\/acs.jafc.1c05213","article-title":"Erythritol Improves Nonalcoholic Fatty Liver Disease by Activating Nrf2 Antioxidant Capacity","volume":"69","author":"Jin","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Wang, Y., Chen, C., Chen, J., Sang, T., Peng, H., Lin, X., Zhao, Q., Chen, S., Eling, T., and Wang, X. (2022). Overexpression of NAG-1\/GDF15 prevents hepatic steatosis through inhibiting oxidative stress-mediated dsDNA release and AIM2 inflammasome activation. Redox Biol., 52.","DOI":"10.1016\/j.redox.2022.102322"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1002\/ptr.6902","article-title":"Apple polyphenol extract alleviates lipid accumulation in free-fatty-acid-exposed HepG2 cells via activating autophagy mediated by SIRT1\/AMPK signaling","volume":"35","author":"Li","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Liu, X., Hu, M., Ye, C., Liao, L., Ding, C., Sun, L., Liang, J., and Chen, Y. (2022). Isosilybin regulates lipogenesis and fatty acid oxidation via the AMPK\/SREBP-1c\/PPARalpha pathway. Chem. Biol. Interact., 368.","DOI":"10.1016\/j.cbi.2022.110250"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"113655","DOI":"10.1016\/j.yexcr.2023.113655","article-title":"Oleic acid improves hepatic lipotoxicity injury by alleviating autophagy dysfunction","volume":"429","author":"Liu","year":"2023","journal-title":"Exp. Cell Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1007\/s11010-022-04619-6","article-title":"Rhamnetin ameliorates non-alcoholic steatosis and hepatocellular carcinoma in vitro","volume":"478","author":"Shatta","year":"2023","journal-title":"Mol. Cell Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.plefa.2011.06.002","article-title":"Docosapentaenoic acid (22:5n-3) down-regulates the expression of genes involved in fat synthesis in liver cells","volume":"85","author":"Kaur","year":"2011","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.tem.2016.06.005","article-title":"The Sweet Path to Metabolic Demise: Fructose and Lipid Synthesis","volume":"27","author":"Herman","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jhep.2021.02.027","article-title":"Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial","volume":"75","author":"Hochuli","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1080\/10408363.2019.1711360","article-title":"Fructose and hepatic insulin resistance","volume":"57","author":"Softic","year":"2020","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1002\/hep.30251","article-title":"Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis","volume":"69","author":"Younossi","year":"2019","journal-title":"Hepatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/s41589-018-0132-2","article-title":"Enzyme promiscuity drives branched-chain fatty acid synthesis in adipose tissues","volume":"14","author":"Wallace","year":"2018","journal-title":"Nat. Chem. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13033","DOI":"10.1096\/fj.202000546R","article-title":"Betulinic acid improves nonalcoholic fatty liver disease through YY1\/FAS signaling pathway","volume":"34","author":"Mu","year":"2020","journal-title":"FASEB J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1002\/hep.32045","article-title":"Fatty Acid Synthase-Suppressor Screening Identifies Sorting Nexin 8 as a Therapeutic Target for NAFLD","volume":"74","author":"Hu","year":"2021","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1053\/j.gastro.2021.07.025","article-title":"TVB-2640 (FASN Inhibitor) for the Treatment of Nonalcoholic Steatohepatitis: FASCINATE-1, a Randomized, Placebo-Controlled Phase 2a Trial","volume":"161","author":"Loomba","year":"2021","journal-title":"Gastroenterology"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/18\/6714\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:53:57Z","timestamp":1760129637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/18\/6714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,20]]},"references-count":44,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["molecules28186714"],"URL":"https:\/\/doi.org\/10.3390\/molecules28186714","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,20]]}}}