{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:30:55Z","timestamp":1760149855426,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81473114","81891012"],"award-info":[{"award-number":["81473114","81891012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inosine 5\u2032-monophoaphate (IMP) is a food additive that promotes serious lipohyperplasia in the liver of C57\/KsJ-db\/db (db\/db) mice. Thus, IMP\u00a0taken orally by healthy mice might also damage\u00a0their health. To date, how IMP affects health after being taken by healthy animals\u00a0is still\u00a0unclear. Therefore, we investigated the health of C57BL\/6J mice affected by IMP intake. Our data revealed that C57BL\/6J mice administered 255 \u03bcM IMP daily via oral gavage for 4 months caused hyperlipidemia and an increase in body fat rate. The expressions of acetyl-CoA carboxylase 1 (ACC1) and phosphorylated acetyl-CoA carboxylase 2 (ACC2) in hepatocytes increased though the administration of IMP, promoting the phosphorylation of adenosine 5\u2032-monophosphate-activated protein kinase (AMPK). The conversion of acetyl-CoA into triglycerides (TGs) was promoted by ACC1. These TGs were transported from the hepatocytes to avoid the development of non-alcoholic fatty liver disease (NAFLD), causing a deficiency of acetyl-CoA in the liver, and then, the increased phosphorylated ACC2 promoted the cytoplasm fatty acids entering the mitochondria and conversion into acetyl-CoA through the fatty acid \u03b2-oxidation pathway, causing a deficiency in fatty acids. Therefore, the liver showed enhanced absorption of exogenous fatty acids, which were converted into TGs, causing lipohyperplasia. In conclusion, an excessive IMP intake promotes metabolic dysfunction in adipose tissue.<\/jats:p>","DOI":"10.3390\/ijms241914588","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T03:04:18Z","timestamp":1695783858000},"page":"14588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Oral Intake of Inosine 5\u2032-Monophosphate in Mice Promotes the Absorption of Exogenous Fatty Acids and Their Conversion into Triglycerides though Enhancing the Phosphorylation of Adenosine 5\u2032-Monophosphate-Activated Protein Kinase in the Liver, Leading to Lipohyperplasia"],"prefix":"10.3390","volume":"24","author":[{"given":"Bin","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongming","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/j.1749-6632.1998.tb10598.x","article-title":"Molecular and physiological evidence for glutamate (umami) taste transduction via a G protein-coupled receptor","volume":"855","author":"Chaudhari","year":"1998","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"931S","DOI":"10.1093\/jn\/130.4.931S","article-title":"Physiological studies on umami taste","volume":"130","author":"Kurihara","year":"2000","journal-title":"J. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"753S","DOI":"10.3945\/ajcn.2009.27462K","article-title":"Umami taste transduction mechanisms","volume":"90","author":"Kinnamon","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.procbio.2013.06.025","article-title":"Biotechnological production of feed nucleotides by microbial strain improvement","volume":"48","author":"Santos","year":"2013","journal-title":"Process Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0300-483X(74)90009-2","article-title":"Safety evaluation of disodium 5\u2032-inosinate, disodium 5\u2032-guanylate and disodium 5\u2032-ribonucleotide","volume":"2","author":"Kojima","year":"1974","journal-title":"Toxicology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.celrep.2015.08.072","article-title":"Adenylosuccinate Is an Insulin Secretagogue Derived from Glucose-Induced Purine Metabolism","volume":"13","author":"Gooding","year":"2015","journal-title":"Cell Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1080\/15257770.2016.1200075","article-title":"Summary of the 2015 Purine and Pyrimidine Society\/Purine Metabolic Patients Association H. Anne Simmonds Memorial Lecture","volume":"35","author":"Becker","year":"2016","journal-title":"Nucleosides Nucleotides Nucleic Acids"},{"key":"ref_8","first-page":"150","article-title":"The freshener inosine 5\u2032-monophosphate disodium aggravates lipid metabolic disorder in elderly db\/db mice","volume":"42","author":"Jiang","year":"2021","journal-title":"Food Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Guo, W., Ge, X., Lu, J., Xu, X., Gao, J., Wang, Q., Song, C., Zhang, Q., and Yu, C. (2022). Diet and Risk of Non-Alcoholic Fatty Liver Disease, Cirrhosis, and Liver Cancer: A Large Prospective Cohort Study in UK Biobank. Nutrients, 14.","DOI":"10.3390\/nu14245335"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"149452","DOI":"10.1155\/2013\/149452","article-title":"Animal models of diabetic neuropathy: Progress since 1960s","volume":"2013","author":"Islam","year":"2013","journal-title":"J. Diabetes Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/cts.13458","article-title":"Using an animal model to predict the effective human dose for oral multiple sclerosis drugs","volume":"16","author":"Liu","year":"2023","journal-title":"Clin. Transl. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"368504211016935","DOI":"10.1177\/00368504211016935","article-title":"Body surface area-based equivalent dose calculation in tree shrew","volume":"104","author":"Xia","year":"2021","journal-title":"Sci. Prog."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1038\/s42255-021-00454-z","article-title":"Umami-induced obesity and metabolic syndrome is mediated by nucleotide degradation and uric acid generation","volume":"3","author":"Cicerchi","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.tem.2015.11.007","article-title":"Daily Eating Patterns and Their Impact on Health and Disease","volume":"27","author":"Zarrinpar","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16647","DOI":"10.1073\/pnas.1413965111","article-title":"Meal frequency and timing in health and disease","volume":"111","author":"Mattson","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0020-1383(97)00057-0","article-title":"Plasma cytokines and endotoxin levels in patients with severe injury and their relationship with organ damage","volume":"28","author":"Jiang","year":"1997","journal-title":"Injury"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7773","DOI":"10.1096\/fj.202000194R","article-title":"Characterization of the variability in the extent of nonalcoholic fatty liver induced by a high-fat diet in the genetically diverse Collaborative Cross mouse model","volume":"34","author":"Tryndyak","year":"2020","journal-title":"FASEB J."},{"key":"ref_18","first-page":"240","article-title":"Adenylosuccinate, a metabolite in purine salvage pathway, binds to AMP-activated protein kinase (AMPK) \u03b3 subunit and enhances the metabolic efficiency of lipid","volume":"15","author":"Wang","year":"2020","journal-title":"Chin. Med. Biotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-1-4939-7598-3_12","article-title":"Compound C\/Dorsomorphin: Its Use and Misuse as an AMPK Inhibitor","volume":"1732","author":"Dasgupta","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrd1112","article-title":"Lovastatin and beyond: The history of the HMG-CoA reductase inhibitors","volume":"2","author":"Tobert","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41586-018-0201-4","article-title":"Structural basis for regulation of human acetyl-CoA carboxylase","volume":"558","author":"Hunkeler","year":"2018","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"836058","DOI":"10.3389\/fonc.2022.836058","article-title":"Acetyl-CoA Carboxylases and Diseases","volume":"12","author":"Wang","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BST20210579","article-title":"New appreciation for an old pathway: The Lands Cycle moves into new arenas in health and disease","volume":"50","year":"2022","journal-title":"Biochem. Soc. Trans."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pang, Y., Xu, X., Xiang, X., Li, Y., Zhao, Z., Li, J., Gao, S., Liu, Q., Mai, K., and Ai, Q. (2021). High Fat Activates O-GlcNAcylation and Affects AMPK\/ACC Pathway to Regulate Lipid Metabolism. Nutrients, 13.","DOI":"10.3390\/nu13061740"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/s41586-022-04787-x","article-title":"ATGL is a biosynthetic enzyme for fatty acid esters of hydroxy fatty acids","volume":"606","author":"Patel","year":"2022","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1194\/jlr.M050062","article-title":"Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL\/6J mice","volume":"55","author":"Tripathy","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"iyad031","DOI":"10.1093\/genetics\/iyad031","article-title":"The Gene Ontology knowledgebase in 2023","volume":"224","author":"Aleksander","year":"2023","journal-title":"Genetics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/pro.4172","article-title":"KEGG mapping tools for uncovering hidden features in biological data","volume":"31","author":"Kanehisa","year":"2022","journal-title":"Protein Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.imlet.2021.05.007","article-title":"Complement System in Alcohol-Associated Liver Disease","volume":"236","author":"Carneiro","year":"2021","journal-title":"Immunol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.cca.2016.12.017","article-title":"Complement in autoimmune diseases","volume":"465","author":"Vignesh","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1542\/pir.2019-0053","article-title":"Hyperlipidemia","volume":"41","author":"Stewart","year":"2020","journal-title":"Pediatr. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1097\/MOP.0b013e32831a6bed","article-title":"Hyperlipidemia, eating disorders, and smoking cessation","volume":"20","author":"Chanoine","year":"2008","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.lfs.2015.10.025","article-title":"Men and mice: Relating their ages","volume":"152","author":"Dutta","year":"2016","journal-title":"Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1093\/ced\/llad182","article-title":"Obesity and Hidradenitis Suppurativa: Targeting meta-inflammation for therapeutic gain?","volume":"48","author":"Mintoff","year":"2023","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"104820","DOI":"10.1016\/j.jprot.2023.104820","article-title":"TMT proteomics analysis of cerebrospinal fluid from patients with cerebral venous sinus thrombosis","volume":"275","author":"Liu","year":"2023","journal-title":"J. Proteom."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14588\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:58:56Z","timestamp":1760129936000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/19\/14588"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,26]]},"references-count":35,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["ijms241914588"],"URL":"https:\/\/doi.org\/10.3390\/ijms241914588","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2023,9,26]]}}}