{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:06:46Z","timestamp":1793747206495,"version":"4.6.1"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T00:00:00Z","timestamp":1735257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32270751"],"award-info":[{"award-number":["32270751"]}]},{"name":"National Natural Science Foundation of China","award":["82371571"],"award-info":[{"award-number":["82371571"]}]},{"name":"National Natural Science Foundation of China","award":["2024KY239"],"award-info":[{"award-number":["2024KY239"]}]},{"name":"National Natural Science Foundation of China","award":["LQ24C070003"],"award-info":[{"award-number":["LQ24C070003"]}]},{"name":"National Natural Science Foundation of China","award":["LY24H250002"],"award-info":[{"award-number":["LY24H250002"]}]},{"name":"health commission of Zhejiang Province of China","award":["32270751"],"award-info":[{"award-number":["32270751"]}]},{"name":"health commission of Zhejiang Province of China","award":["82371571"],"award-info":[{"award-number":["82371571"]}]},{"name":"health commission of Zhejiang Province of China","award":["2024KY239"],"award-info":[{"award-number":["2024KY239"]}]},{"name":"health commission of Zhejiang Province of China","award":["LQ24C070003"],"award-info":[{"award-number":["LQ24C070003"]}]},{"name":"health commission of Zhejiang Province of China","award":["LY24H250002"],"award-info":[{"award-number":["LY24H250002"]}]},{"name":"Natural Science Foundation of Zhejiang Province of China","award":["32270751"],"award-info":[{"award-number":["32270751"]}]},{"name":"Natural Science Foundation of Zhejiang Province of China","award":["82371571"],"award-info":[{"award-number":["82371571"]}]},{"name":"Natural Science Foundation of Zhejiang Province of China","award":["2024KY239"],"award-info":[{"award-number":["2024KY239"]}]},{"name":"Natural Science Foundation of Zhejiang Province of China","award":["LQ24C070003"],"award-info":[{"award-number":["LQ24C070003"]}]},{"name":"Natural Science Foundation of Zhejiang Province of China","award":["LY24H250002"],"award-info":[{"award-number":["LY24H250002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: UFMylation, a newly identified ubiquitin-like modification, modulates a variety of physiological processes, including endoplasmic reticulum homeostasis maintenance, DNA damage response, embryonic development, and tumor progression. Recent reports showed that UFMylation plays a protective role in preventing liver steatosis and fibrosis, serving as a defender of liver homeostasis in the development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the regulation of UFMylation in MASLD remains unclear. This study aimed to determine the expressed patterns of UFMylation components in multiple tissues of leptin-deficient ob\/ob mice and high-fat diet (HFD)-fed mice, which are mimicking the conditions of MASLD. Methods: The ob\/ob mice and HFD-fed mice were sacrificed to collect tissues indicated in this study. Total RNA and proteins were extracted from tissues to examine the expressed patterns of UFMylation components, including UBA5, UFC1, UFL1, DDRGK1, UFSP1, UFSP2 and UFM1, by real-time PCR and western blot analysis. Results: The protein levels of UBA5, UFC1 and UFL1 were down-regulated in liver, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT), whereas the messenger RNA (mRNA) levels of Ufl1 and Ufsp1 were both decreased in skeletal muscle, BAT, iWAT and epididymal white adipose tissue (eWAT) of ob\/ob mice. In contrast, the mRNA levels of Ufsp1 in skeletal muscle, BAT, iWAT and heart, and the protein levels of UFL1 were decreased in BAT, iWAT, heart and cerebellum of HFD-fed mice. Conclusions: Our findings established the expressed profiles of UFMylaiton in multiple tissues of mice mimicking MASLD, indicating an important regulation for UFMylation in these tissues\u2019 homeostasis maintenance.<\/jats:p>","DOI":"10.3390\/genes16010031","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T12:37:19Z","timestamp":1735648639000},"page":"31","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Systematic Analysis of UFMylation Family Genes in Tissues of Mice with Metabolic Dysfunction-Associated Steatotic Liver Disease"],"prefix":"10.3390","volume":"16","author":[{"given":"Mingdi","family":"Jiang","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenlu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Duan","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaiyong","family":"Qi","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Zeng","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabao","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9192-3622","authenticated-orcid":false,"given":"Jiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Medical Epigenetics, Department of Cell Biology and Genetics, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou 310036, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100485","DOI":"10.1016\/j.jlr.2023.100485","article-title":"From NAFLD to MASLD: Updated naming and diagnosis criteria for fatty liver disease","volume":"65","author":"Rinella","year":"2024","journal-title":"J. Lipid Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6571","DOI":"10.3748\/wjg.v23.i36.6571","article-title":"Nonalcoholic fatty liver disease: Evolving paradigms","volume":"23","author":"Lonardo","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1016\/j.cmet.2019.02.012","article-title":"Phosphoproteomics Reveals the GSK3-PDX1 Axis as a Key Pathogenic Signaling Node in Diabetic Islets","volume":"29","author":"Sacco","year":"2019","journal-title":"Cell Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1309\/4UBB-BF78-F55V-50KA","article-title":"Ubiquitin as a marker of cell injury in nonalcoholic steatohepatitis","volume":"114","author":"Banner","year":"2000","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/hep.30822","article-title":"Hepatocyte TNF Receptor-Associated Factor 6 Aggravates Hepatic Inflammation and Fibrosis by Promoting Lysine 6-Linked Polyubiquitination of Apoptosis Signal-Regulating Kinase 1","volume":"71","author":"Wang","year":"2020","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/hep.28933","article-title":"Deregulated neddylation in liver fibrosis","volume":"65","author":"Simon","year":"2017","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1038\/sj.emboj.7600205","article-title":"A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier","volume":"23","author":"Komatsu","year":"2004","journal-title":"EMBO J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5417","DOI":"10.1074\/jbc.M109.036814","article-title":"A novel type of E3 ligase for the Ufm1 conjugation system","volume":"285","author":"Tatsumi","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"111168","DOI":"10.1016\/j.celrep.2022.111168","article-title":"Human UFSP1 is an active protease that regulates UFM1 maturation and UFMylation","volume":"40","author":"Millrine","year":"2022","journal-title":"Cell Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.molcel.2014.08.007","article-title":"Modification of ASC1 by UFM1 is crucial for ERalpha transactivation and breast cancer development","volume":"56","author":"Yoo","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1093\/nar\/gkz110","article-title":"MRE11 UFMylation promotes ATM activation","volume":"47","author":"Wang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1038\/s41467-019-09175-0","article-title":"UFL1 promotes histone H4 ufmylation and ATM activation","volume":"10","author":"Qin","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/s41556-020-0559-z","article-title":"UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination","volume":"22","author":"Liu","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2119531119","DOI":"10.1073\/pnas.2119531119","article-title":"Signaling from the RNA sensor RIG-I is regulated by ufmylation","volume":"119","author":"Snider","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7857","DOI":"10.1038\/s41467-022-35501-0","article-title":"The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3","volume":"13","author":"Ishimura","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e2215732120","DOI":"10.1073\/pnas.2215732120","article-title":"Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and identified as a potential therapeutic target","volume":"120","author":"Zhou","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1172\/JCI90193","article-title":"Loss of DDRGK1 modulates SOX9 ubiquitination in spondyloepimetaphyseal dysplasia","volume":"127","author":"Egunsola","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.jgg.2021.04.006","article-title":"Ufl1 deficiency causes kidney atrophy associated with disruption of endoplasmic reticulum homeostasis","volume":"48","author":"Zhou","year":"2021","journal-title":"J. Genet. Genom."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e004917","DOI":"10.1161\/CIRCHEARTFAILURE.118.004917","article-title":"Ufm1-Specific Ligase Ufl1 Regulates Endoplasmic Reticulum Homeostasis and Protects Against Heart Failure","volume":"11","author":"Li","year":"2018","journal-title":"Circ. Heart Fail."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.ajhg.2016.06.020","article-title":"Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy","volume":"99","author":"Muona","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.ajhg.2016.06.030","article-title":"Biallelic Variants in UBA5 Reveal that Disruption of the UFM1 Cascade Can Result in Early-Onset Encephalopathy","volume":"99","author":"Colin","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1093\/brain\/awy135","article-title":"Biallelic UFM1 and UFC1 mutations expand the essential role of ufmylation in brain development","volume":"141","author":"Nahorski","year":"2018","journal-title":"Brain"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Duan, R., Shi, Y., Yu, L., Zhang, G., Li, J., Lin, Y., Guo, J., Wang, J., Shen, L., and Jiang, H. (2016). UBA5 Mutations Cause a New Form of Autosomal Recessive Cerebellar Ataxia. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149039"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Jing, Y., Mao, Z., and Chen, F. (2022). UFMylation System: An Emerging Player in Tumorigenesis. Cancers, 14.","DOI":"10.3390\/cancers14143501"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.yexmp.2014.05.010","article-title":"Ufmylation and FATylation pathways are downregulated in human alcoholic and nonalcoholic steatohepatitis, and mice fed DDC, where Mallory-Denk bodies (MDBs) form","volume":"97","author":"Liu","year":"2014","journal-title":"Exp. Mol. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.yexmp.2014.10.001","article-title":"Mallory-Denk Body (MDB) formation modulates Ufmylation expression epigenetically in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH)","volume":"97","author":"Liu","year":"2014","journal-title":"Exp. Mol. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/s41419-023-06095-2","article-title":"Ufmylation on UFBP1 alleviates non-alcoholic fatty liver disease by modulating hepatic endoplasmic reticulum stress","volume":"14","author":"Mao","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Li, X., and Wang, H. (2020). Multiple organs involved in the pathogenesis of non-alcoholic fatty liver disease. Cell Biosci., 10.","DOI":"10.1186\/s13578-020-00507-y"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.molcel.2024.01.024","article-title":"UFL1 ablation in T cells suppresses PD-1 UFMylation to enhance anti-tumor immunity","volume":"84","author":"He","year":"2024","journal-title":"Mol. Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molcel.2008.03.003","article-title":"AMPK phosphorylation of raptor mediates a metabolic checkpoint","volume":"30","author":"Gwinn","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s13046-023-02681-6","article-title":"Loss of Ufl1\/Ufbp1 in hepatocytes promotes liver pathological damage and carcinogenesis through activating mTOR signaling","volume":"42","author":"Chen","year":"2023","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, X., Xu, X., and Wang, Z. (2023). The Post-Translational Role of UFMylation in Physiology and Disease. Cells, 12.","DOI":"10.3390\/cells12212543"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fang, B., Li, Z., Qiu, Y., Cho, N., and Yoo, H.M. (2021). Inhibition of UBA5 Expression and Induction of Autophagy in Breast Cancer Cells by Usenamine A. Biomolecules, 11.","DOI":"10.3390\/biom11091348"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/1\/31\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:01:43Z","timestamp":1760115703000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/1\/31"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,27]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["genes16010031"],"URL":"https:\/\/doi.org\/10.3390\/genes16010031","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,27]]}}}