{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:16:21Z","timestamp":1782818181110,"version":"3.54.5"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T00:00:00Z","timestamp":1668384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Drug treatment of metabolic associated fatty liver disease (MAFLD) remains lacking. This study analyzes the efficacy and mechanism underlying intermittent fasting combined with lipidomics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty-two male rats were randomly divided into three groups: Normal group, administered a standard diet; MAFLD group, administered a 60% high-fat diet; time-restricted feeding (TRF) group, administered a 60% high-fat diet. Eating was allowed for 6 h per day (16:00\u201322:00). After 15 weeks, liver lipidomics and other indicators were compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 1,062 metabolites were detected. Compared with the Normal group, the weight, body fat ratio, aspartate aminotransferase, total cholesterol, low-density cholesterol, fasting blood glucose, uric acid, and levels of 317 lipids including triglycerides (TG) (17:0<jats:sub>\u2212<\/jats:sub>18:1<jats:sub>\u2212<\/jats:sub>20:4) were upregulated, whereas the levels of 265 lipids including phosphatidyl ethanolamine (PE) (17:0<jats:sub>\u2212<\/jats:sub>20:5) were downregulated in the MAFLD group (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Compared with the MAFLD group, the weight, body fat ratio, daily food intake, and levels of 253 lipids including TG (17:0<jats:sub>\u2212<\/jats:sub>18:1<jats:sub>\u2212<\/jats:sub>22:5) were lower in the TRF group. Furthermore, the levels of 82 lipids including phosphatidylcholine (PC) (20:4<jats:sub>\u2212<\/jats:sub>22:6) were upregulated in the TRF group (<jats:italic>P<\/jats:italic> &amp;lt; 0.05), while serum TG level was increased; however, the increase was not significant (<jats:italic>P<\/jats:italic> &amp;gt; 0.05). Enrichment analysis of differential metabolites showed that the pathways associated with the observed changes mainly included metabolic pathways, regulation of lipolysis in adipocytes, and fat digestion and absorption, while reverse-transcription polymerase chain reaction showed that TRF improved the abnormal expression of <jats:italic>FAS<\/jats:italic> and <jats:italic>PPAR<\/jats:italic>\u03b1 genes in the MAFLD group (<jats:italic>P<\/jats:italic> &amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results suggest that 6 h of TRF can improve MAFLD <jats:italic>via<\/jats:italic> reducing food intake by 13% and improving the expression of genes in the PPAR\u03b1\/FAS pathway, thereby providing insights into the prevention and treatment of MAFLD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2022.838091","type":"journal-article","created":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T06:10:30Z","timestamp":1668406230000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy and mechanism of intermittent fasting in metabolic associated fatty liver disease based on ultraperformance liquid chromatography-tandem mass spectrometry"],"prefix":"10.3389","volume":"9","author":[{"given":"Jiang","family":"Deng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengnan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenrui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangsuo","family":"Dang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanjuan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,11,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","first-page":"Itc65","DOI":"10.7326\/IsTranslatedFrom_AITC201811060_Japanese","article-title":"Nonalcoholic fatty liver disease","volume":"169","author":"Wang","year":"2018","journal-title":"Ann Intern Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1097\/MEG.0000000000001235","article-title":"Nonalcoholic fatty liver disease: current concepts, epidemiology and management strategies","volume":"30","author":"Tomic","year":"2018","journal-title":"Euro J Gastroenterol Hepatol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1002\/hep.30702","article-title":"Unexpected rapid increase in the burden of NAFLD in China from 2008 to 2018: a systematic review and meta-analysis","volume":"70","author":"Zhou","year":"2019","journal-title":"Hepatology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1111\/acel.12128","article-title":"Liver diseases and aging: friends or foes?","volume":"12","author":"Sheedfar","year":"2013","journal-title":"Aging Cell."},{"key":"B6","doi-asserted-by":"publisher","first-page":"195","DOI":"10.3969\/j.issn.1001\u20135256.2018.05.007","article-title":"Guidelines for the prevention and treatment of nonalcoholic fatty liver disease (2018 update)","volume":"26","year":"2018","journal-title":"J Clin Hepatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2442","DOI":"10.3390\/nu11102442","article-title":"Effectiveness of intermittent fasting and time-restricted feeding compared to continuous energy restriction for weight loss","volume":"11","author":"Rynders","year":"2019","journal-title":"Nutrients."},{"key":"B8","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.cmet.2017.08.019","article-title":"Intermittent fasting promotes white adipose browning and decreases obesity by shaping the gut microbiota","volume":"26","author":"Li","year":"2017","journal-title":"Cell Metab"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1056\/NEJMc2001176","article-title":"Effects of intermittent fasting on health, aging, and disease","volume":"382","author":"Saad","year":"2020","journal-title":"N Engl J Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"5168","DOI":"10.1111\/jcmm.15166","article-title":"A network pharmacology-based approach to explore the effects of Chaihu Shugan powder on a non-alcoholic fatty liver rat model through nuclear receptors","volume":"24","author":"Nie","year":"2020","journal-title":"J Cell Mol Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"118986","DOI":"10.1016\/j.lfs.2020.118986","article-title":"Transcriptome analysis reveals the efficacy of ginsenoside-Rg1 in the treatment of nonalcoholic fatty liver disease","volume":"267","author":"Gu","year":"2021","journal-title":"Life Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"8284107","DOI":"10.1155\/2018\/8284107","article-title":"Protective effects of taraxasterol against ethanol-induced liver injury by regulating CYP2E1\/Nrf2\/HO-1 and NF-\u03baB signaling pathways in mice","volume":"2018","author":"Xu","year":"2018","journal-title":"Oxid Med Cell Longev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"7608","DOI":"10.1021\/acs.analchem.8b01331","article-title":"Development of a high coverage pseudotargeted lipidomics method based on ultra-high performance liquid chromatography-mass spectrometry","volume":"90","author":"Xuan","year":"2018","journal-title":"Anal Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.chroma.2016.02.054","article-title":"Comprehensive untargeted lipidomic analysis using core-shell C30 particle column and high field orbitrap mass spectrometer","volume":"1440","author":"Narv\u00e1ez-Rivas","year":"2016","journal-title":"J Chromatogr A."},{"key":"B15","doi-asserted-by":"publisher","first-page":"6142","DOI":"10.1021\/acs.jafc.0c01778","article-title":"Hepatic lipidomics analysis reveals the antiobesity and cholesterol-lowering effects of tangeretin in high-fat diet-fed rats","volume":"68","author":"Feng","year":"2020","journal-title":"J Agric Food Chem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1111\/1751-2980.12431","article-title":"The role of ADIPOQ methylation in curcumin-administrated experimental nonalcoholic fatty liver disease","volume":"17","author":"Chen","year":"2016","journal-title":"J Dig Dis."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e3000622","DOI":"10.1371\/journal.pbio.3000622","article-title":"Eating breakfast and avoiding late-evening snacking sustains lipid oxidation","volume":"18","author":"Kelly","year":"2020","journal-title":"PLoS Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1038\/s41586-021-03827-2","article-title":"Dietary fructose improves intestinal cell survival and nutrient absorption","volume":"597","author":"Taylor","year":"2021","journal-title":"Nature."},{"key":"B19","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1002\/oby.22065","article-title":"Mainous 3rd AG, et al. Flipping the metabolic switch: understanding and applying the health benefits of fasting","volume":"26","author":"Anton","year":"2018","journal-title":"Obesity."},{"key":"B20","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1038\/s41467-020-14676-4","article-title":"Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment","volume":"11","author":"Liu","year":"2020","journal-title":"Nat Commun."},{"key":"B21","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.cmet.2018.08.011","article-title":"Daily fasting improves health and survival in male mice independent of diet composition and calories","volume":"29","author":"Mitchell","year":"2019","journal-title":"Cell Metab"},{"key":"B22","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41387-021-00149-0","article-title":"Effect of time restricted eating on body weight and fasting glucose in participants with obesity: results of a randomized, controlled, virtual clinical trial","volume":"11","author":"Peeke","year":"2021","journal-title":"Nutr Diabetes."},{"key":"B23","doi-asserted-by":"publisher","first-page":"718936","DOI":"10.3389\/fnut.2021.718936","article-title":"Time-restricted feeding and aerobic performance in elite runners: Ramadan fasting as a model","volume":"8","author":"Al-Nawaiseh","year":"2021","journal-title":"Front Nutr."},{"key":"B24","doi-asserted-by":"publisher","first-page":"113313","DOI":"10.1016\/j.physbeh.2021.113313","article-title":"Time-restricted feeding attenuates gluconeogenic activity through inhibition of PGC-1\u03b1 expression and activity","volume":"231","author":"She","year":"2021","journal-title":"Physiol Behav."},{"key":"B25","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s11883-021-00922-7","article-title":"Time-restricted eating to improve cardiovascular health","volume":"23","author":"Gabel","year":"2021","journal-title":"Curr Atheroscler Rep."},{"key":"B26","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.cmet.2013.12.016","article-title":"Circadian clocks and feeding time regulate the oscillations and levels of hepatic triglycerides","volume":"19","author":"Adamovich","year":"2014","journal-title":"Cell Metab."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3932491","DOI":"10.1155\/2017\/3932491","article-title":"Impact of time-restricted feeding and dawn-to-sunset fasting on circadian rhythm, obesity, metabolic syndrome, and nonalcoholic fatty liver disease","volume":"17","author":"Mindikoglu","year":"2017","journal-title":"Gastroenterol Res Pract."},{"key":"B28","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1016\/j.cmet.2012.04.019","article-title":"Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet","volume":"15","author":"Hatori","year":"2012","journal-title":"Cell Metab."},{"key":"B29","doi-asserted-by":"publisher","first-page":"596285","DOI":"10.3389\/fnut.2020.596285","article-title":"Time-restricted feeding reduces the detrimental effects of a high-fat diet, possibly by modulating the circadian rhythm of hepatic lipid metabolism and gut microbiota","volume":"7","author":"Ye","year":"2020","journal-title":"Front Nutr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1016\/j.cmet.2018.04.010","article-title":"Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes","volume":"27","author":"Sutton","year":"2018","journal-title":"Cell Metab"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e926789","DOI":"10.12659\/MSM.926789","article-title":"Intermittent fasting improves lipid metabolism through changes in gut microbiota in diet-induced obese mice","volume":"26","author":"Deng","year":"2020","journal-title":"Med Sci Monit."},{"key":"B32","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1210\/er.2018-00064","article-title":"Molecular actions of PPAR\u03b1 in lipid metabolism and inflammation","volume":"39","author":"Bougarne","year":"2018","journal-title":"Endocr Rev."},{"key":"B33","doi-asserted-by":"publisher","first-page":"5847","DOI":"10.1038\/s41467-020-19554-7","article-title":"Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting","volume":"11","author":"Brocker","year":"2020","journal-title":"Nat Commun."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.1194\/jlr.M088419","article-title":"Extrahepatic PPAR\u03b1 modulates fatty acid oxidation and attenuates fasting-induced hepatosteatosis in mice","volume":"59","author":"Brocker","year":"2018","journal-title":"J Lipid Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/978-3-319-48382-5_19","article-title":"Non-alcoholic fatty liver disease","volume":"960","author":"Engin","year":"2017","journal-title":"Adv Exp Med Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"13033","DOI":"10.1096\/fj.202000546R","article-title":"Betulinic acid improves non-alcoholic fatty liver disease through YY1\/FAS signaling pathway","volume":"34","author":"Mu","year":"2020","journal-title":"FASEB J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1186\/s12906-019-2671-9","article-title":"Diosgenin ameliorates palmitic acid-induced lipid accumulation via AMPK\/ACC\/CPT-1A and SREBP-1c\/FAS signaling pathways in LO2 cells","volume":"19","author":"Fang","year":"2019","journal-title":"BMC Complement Altern Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-4020-8831-5_1","article-title":"Transcriptional regulation of hepatic fatty acid metabolism","volume":"49","author":"Guillou","year":"2008","journal-title":"Subcell Biochem."},{"key":"B39","doi-asserted-by":"publisher","first-page":"158519","DOI":"10.1016\/j.bbalip.2019.158519","article-title":"Exercise regulates lipid droplet dynamics in normal and fatty liver","volume":"1864","author":"la Fuente","year":"2019","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"B40","doi-asserted-by":"publisher","first-page":"108531","DOI":"10.1016\/j.jnutbio.2020.108531","article-title":"Time-restricted feeding mice a high-fat diet induces a unique lipidomic profile","volume":"88","author":"Mehus","year":"2021","journal-title":"J Nutr Biochem."},{"key":"B41","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1538\/expanim.20-0112","article-title":"Time-restricted feeding prevents high-fat and high-cholesterol diet-induced obesity but fails to ameliorate atherosclerosis in apolipoprotein E-knockout mice","volume":"70","author":"Inoue","year":"2021","journal-title":"Exp Anim."},{"key":"B42","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1038\/s41467-020-20743-7","article-title":"Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models","volume":"12","author":"Das","year":"2021","journal-title":"Nat Commun."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.838091\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T06:10:33Z","timestamp":1668406233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.838091\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,14]]},"references-count":42,"alternative-id":["10.3389\/fnut.2022.838091"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.838091","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,14]]},"article-number":"838091"}}