{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:10:17Z","timestamp":1790719817679,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: The neutrophilic peptide, alpha-defensin, is considered an evolving risk factor intimately linked with lipid mobilization. It was previously linked to augmented liver fibrosis. Here, we assess a potential association between alpha-defensin and fatty liver. Materials and Methods: A cohort of transgenic C57BL\/6JDef+\/+ male mice that overexpress the human neutrophil-derived alpha-defensin in their polymorphonuclear neutrophils (PMNs) were assessed for liver steatosis and fibrosis development. Wild type (C57BL\/6JDef.Wt) and transgenic (C57BL\/6JDef+\/+) mice were maintained on a standard rodent chow diet for 8.5 months. At the termination of the experiment, systemic metabolic indices and hepatic immunological cell profiling were assessed. Results: The Def+\/+ transgenic mice exhibited lower body and liver weights, lower serum fasting glucose and cholesterol, and significantly lower liver fat content. These results were associated with impaired liver lymphocytes count and function (lower CD8, NK cells, and killing marker CD107a). The metabolic cage demonstrated dominant fat utilization with a comparable food intake in the Def+\/+ mice. Conclusions: Chronic physiological expression of alpha-defensin induces favorable blood metabolic profile, increased systemic lipolysis, and decreased hepatic fat accumulation. Further studies are needed to characterize the defensin net liver effect.<\/jats:p>","DOI":"10.3390\/medicina59050983","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T10:35:11Z","timestamp":1684492511000},"page":"983","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Alleviation of Hepatic Steatosis by Alpha-Defensin Is Associated with Enhanced Lipolysis"],"prefix":"10.3390","volume":"59","author":[{"given":"Emad","family":"Maraga","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Hadassah Hebrew University Hospital, Jerusalem IL-91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rifaat","family":"Safadi","sequence":"additional","affiliation":[{"name":"Liver Unit, Hadassah Hebrew University Hospital, Jerusalem IL-91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Amer","sequence":"additional","affiliation":[{"name":"Liver Unit, Hadassah Hebrew University Hospital, Jerusalem IL-91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abd Al-roof","family":"Higazi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Hadassah Hebrew University Hospital, Jerusalem IL-91120, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami Abu","family":"Fanne","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Hadassah Hebrew University Hospital, Jerusalem IL-91120, Israel"},{"name":"Department of Cardiology, Hillel Yaffe Medical Center, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s11892-021-01377-5","article-title":"Genetic Contribution to Non-alcoholic Fatty Liver Disease and Prognostic Implications","volume":"21","author":"Martin","year":"2021","journal-title":"Curr. Diabetes Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Salari, N., Darvishi, N., Mansouri, K., Ghasemi, H., Hosseinian-Far, M., Darvishi, F., and Mohammadi, M. (2021). Association between PNPLA3 rs738409 polymorphism and nonalcoholic fatty liver disease: A systematic review and meta-analysis. BMC Endocr. Disord., 21.","DOI":"10.1186\/s12902-021-00789-4"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Rojano-Toimil, A., Rivera-Esteban, J., Manzano-Nu\u00f1ez, R., Ba\u00f1ares, J., Selva, D.M., Gabriel-Medina, P., Ferrer, R., Peric\u00e0s, J.M., and Ciudin, A. (2022). When Sugar Reaches the Liver: Phenotypes of Patients with Diabetes and NAFLD. J. Clin. Med., 11.","DOI":"10.3390\/jcm11123286"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s00335-016-9658-3","article-title":"Mapping liver fat female-dependent quantitative trait loci in collaborative cross mice","volume":"27","author":"Atamni","year":"2016","journal-title":"Mamm. Genome"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41575-020-00381-6","article-title":"Global epidemiology of NAFLD-related HCC: Trends, predictions, risk factors and prevention","volume":"18","author":"Huang","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Juanola, O., Mart\u00ednez-L\u00f3pez, S., Franc\u00e9s, R., and G\u00f3mez-Hurtado, I. (2021). Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18105227"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cld.2017.08.003","article-title":"The Natural History of Nonalcoholic Fatty Liver Disease-An Evolving View","volume":"22","author":"Lindenmeyer","year":"2018","journal-title":"Clin. Liver Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.21037\/hbsn-21-528","article-title":"Long-term outcomes in patients with non-alcoholic fatty liver disease: Further evidence that a multidisciplinary and patient-centred approach to treatment is needed","volume":"11","author":"Targher","year":"2022","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jitrukthai, S., Kositamongkol, C., Boonchai, P., Mepramoon, E., Ariyakunaphan, P., Nimitpunya, P., Srivanichakorn, W., Chaisathaphol, T., Washirasaksiri, C., and Auesomwang, C. (2022). Long-Term Outcomes Associated with NAFLD, ASCVD, and All-Cause Mortality of Patients with Metabolic Syndrome. J. Clin. Med., 11.","DOI":"10.3390\/jcm11154627"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1056\/NEJMoa2029349","article-title":"Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease","volume":"385","author":"Sanyal","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5114\/ceh.2021.104441","article-title":"Non-alcoholic fatty liver disease and lipotoxicity","volume":"7","author":"Wasilewska","year":"2021","journal-title":"Clin. Exp. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s00335-016-9667-2","article-title":"Glucose tolerance female-specific QTL mapped in collaborative cross mice","volume":"28","author":"Ziner","year":"2017","journal-title":"Mamm. Genome"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.2353\/ajpath.2009.080999","article-title":"Increased hepatic myeloperoxidase activity in obese subjects with nonalcoholic steatohepatitis","volume":"175","author":"Rensen","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/hep.21070","article-title":"Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: Impact on disease progression","volume":"43","author":"Ikura","year":"2006","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Rensen, S.S., Bieghs, V., Xanthoulea, S., Arfianti, E., Bakker, J.A., Shiri-Sverdlov, R., Hofker, M.H., Greve, J.W., and Buurman, W.A. (2012). Neutrophil-derived myeloperoxidase aggravates non-alcoholic steatohepatitis in low-density lipoprotein receptor-deficient mice. PLoS ONE., 7.","DOI":"10.1371\/journal.pone.0052411"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1021\/acs.accounts.6b00653","article-title":"Human \u03b1-Defensin 6: A Small Peptide That Self-Assembles and Protects the Host by Entangling Microbes","volume":"50","author":"Chairatana","year":"2017","journal-title":"Acc. Chem. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"764","DOI":"10.3389\/fimmu.2020.00764","article-title":"Defensins: A Double-Edged Sword in Host Immunity","volume":"11","author":"Xu","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.semcdb.2018.04.006","article-title":"Human antimicrobial peptides and cancer","volume":"88","author":"Jin","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1111\/liv.12203","article-title":"Transgenic expression of human neutrophil peptide-1 enhances hepatic fibrosis in mice fed a choline-deficient, L-amino acid\u2013defined diet","volume":"33","author":"Ibusuki","year":"2013","journal-title":"Liver Intl."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1146\/annurev.immunol.22.012703.104603","article-title":"Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense","volume":"22","author":"Yang","year":"2004","journal-title":"Annu. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1164\/rccm.200907-1128OC","article-title":"Neutrophil \u03b1-defensins cause lung injury by disrupting the capillary-epithelialbarrier","volume":"181","author":"Bdeir","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1074\/jbc.M115.669812","article-title":"\u03b1-Defensins Induce a Post-translational Modification of Low Density Lipoprotein (LDL) That Promotes Atherosclerosis at Normal Levels of Plasma Cholesterol","volume":"291","author":"Maraga","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4440","DOI":"10.1182\/blood-2011-06-362947","article-title":"Serglycin participates in retention of \u03b1-defensin in granules during myelopoiesis","volume":"118","author":"Cowland","year":"2011","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"594853","DOI":"10.3389\/fvets.2020.594853","article-title":"Improved Folch method for liver-fat quantification","volume":"7","author":"Mopuri","year":"2021","journal-title":"Front. Vet. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"194","DOI":"10.32074\/1591-951X-242","article-title":"Pathology of non-alcoholic fatty liver disease","volume":"113","author":"Cataldo","year":"2021","journal-title":"Pathologica"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s00392-020-01709-7","article-title":"NAFLD and cardiovascular diseases: A clinical review","volume":"110","author":"Kasper","year":"2021","journal-title":"Clin. Res. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3491","DOI":"10.1172\/JCI35740","article-title":"Neutrophil primary granule proteins HBP and HNP1\u20133 boost bacterial phagocytosis by human and murine macrophages","volume":"118","author":"Soehnlein","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1161\/ATVBAHA.111.227116","article-title":"Human neutrophil peptides mediate endothelial-monocyte interaction, foam cell formation, and platelet activation","volume":"31","author":"Quinn","year":"2011","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1053\/jhep.2001.29628","article-title":"Gene expression of tumor necrosis factor alpha and TNF receptors, p55 and p75, in nonalcoholic steatohepatitis patients","volume":"34","author":"Crespo","year":"2001","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1111\/jgh.15631","article-title":"Circulating tumor necrosis factor-\u03b1 levels in non-alcoholic fatty liver disease: A systematic review and a meta-analysis","volume":"36","author":"Potoupni","year":"2021","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41419-020-2264-z","article-title":"The concentration of tumor necrosis factor-\u03b1 determines its protective or damaging effect on liver injury by regulating Yap activity","volume":"11","author":"Zhao","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2337\/cd18-0026","article-title":"Patients With Lean Nonalcoholic Fatty Liver Disease Are Metabolically Abnormal and Have a Higher Risk for Mortality","volume":"37","author":"Golabi","year":"2019","journal-title":"Clin. Diabetes"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/5\/983\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:38:30Z","timestamp":1760125110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/59\/5\/983"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,19]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["medicina59050983"],"URL":"https:\/\/doi.org\/10.3390\/medicina59050983","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,19]]}}}