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Although OLFM2 is involved in the regulation of the energy metabolism and OLFM4 is an important player in inflammation, innate immunity and cancer, the role of OLFMs in NAFLD-related intestinal dysbiosis remains unknown. In this study, we analysed the hepatic mRNA expression of OLFM2 and the jejunal expression of OLFM4 in a well-established cohort of women with morbid obesity (MO), classified according to their hepatic histology into normal liver (n = 27), simple steatosis (n = 26) and nonalcoholic steatohepatitis (NASH, n = 16). Our results showed that OLFM2 hepatic mRNA was higher in NASH, in advanced degrees of steatosis and in the presence of lobular inflammation. Additionally, we obtained positive correlations between hepatic OLFM2 and glucose, cholesterol, trimethylamine N-oxide and deoxycholic acid levels and hepatic fatty acid synthase, and negative associations with weight and jejunal Toll-like receptors (TLR4) and TLR5 expression. Regarding jejunal OLFM4, we observed positive correlations with circulating interleukin (IL)-8, IL-10, IL-17 and jejunal TLR9. In conclusion, OLFM2 in the liver seems to play a relevant role in NAFLD progression, while OLFM4 in the jejunum could be involved in gut dysbiosis-related inflammatory events.<\/jats:p>","DOI":"10.3390\/ijms23137442","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T11:15:05Z","timestamp":1656933305000},"page":"7442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["New Insights of OLFM2 and OLFM4 in Gut-Liver Axis and Their Potential Involvement in Nonalcoholic Fatty Liver Disease"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9052-1368","authenticated-orcid":false,"given":"Laia","family":"Bertran","sequence":"first","affiliation":[{"name":"Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV), 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3307-4340","authenticated-orcid":false,"given":"Rosa","family":"Jorba-Martin","sequence":"additional","affiliation":[{"name":"Servei de Cirurgia General i de l\u2019Aparell Digestiu, Hospital Universitari de Tarragona Joan XXIII, Universitat Rovira i Virgili (URV), Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV), Mallafr\u00e9 Guasch, 4, 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9939-1010","authenticated-orcid":false,"given":"Andrea","family":"Barrientos-Riosalido","sequence":"additional","affiliation":[{"name":"Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV), 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6167-9801","authenticated-orcid":false,"given":"Marta","family":"Portillo-Carrasquer","sequence":"additional","affiliation":[{"name":"Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV), 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV), 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Riesco","sequence":"additional","affiliation":[{"name":"Servei Medicina Interna, Hospital Universitari de Tarragona Joan XXIII, Mallafr\u00e9 Guasch, 4, 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salom\u00e9","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Servei Anatomia Patol\u00f2gica, Hospital Universitari de Tarragona Joan XXIII, Mallafr\u00e9 Guasch, 4, 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita","family":"Vives","sequence":"additional","affiliation":[{"name":"Servei de Cirurgia, Hospital Sant Joan de Reus, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV), Avinguda Doctor Josep Laporte, 2, 43204 Reus, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F\u00e0tima","family":"Sabench","sequence":"additional","affiliation":[{"name":"Servei de Cirurgia, Hospital Sant Joan de Reus, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), 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Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0396-6428","authenticated-orcid":false,"given":"Teresa","family":"Auguet","sequence":"additional","affiliation":[{"name":"Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV), 43007 Tarragona, Spain"},{"name":"Servei Medicina Interna, Hospital Universitari de Tarragona Joan XXIII, Mallafr\u00e9 Guasch, 4, 43007 Tarragona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/03602532.2017.1293683","article-title":"Non-Alcoholic Fatty Liver Disease (NAFLD)\u2014Pathogenesis, Classification, and Effect on Drug Metabolizing Enzymes and Transporters","volume":"49","author":"Cobbina","year":"2017","journal-title":"Drug Metab. Rev."},{"key":"ref_2","first-page":"384","article-title":"Non-Alcoholic Fatty Liver Disease: A Clinical Update","volume":"5","author":"Pappachan","year":"2017","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/ar.20715","article-title":"Hepatic Microcirculation in Fatty Liver Disease","volume":"291","author":"Farrell","year":"2008","journal-title":"Anat. Rec. Adv. Integr. Anat. Evol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.cld.2017.08.007","article-title":"Pathophysiology of Nonalcoholic Fatty Liver Disease\/Nonalcoholic Steatohepatitis","volume":"22","author":"Manne","year":"2018","journal-title":"Clin. Liver Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00423-020-01965-1","article-title":"Mechanisms of Nonalcoholic Fatty Liver Disease and Implications for Surgery","volume":"406","author":"Kaufmann","year":"2021","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The Diagnosis and Management of Nonalcoholic Fatty Liver Disease","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2152\/jmi.63.27","article-title":"The Intestinal Microbiota and Its Role in Human Health and Disease","volume":"63","author":"Kataoka","year":"2016","journal-title":"J. Med. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15718","DOI":"10.1073\/pnas.0407076101","article-title":"The Gut Microbiota as an Environmental Factor That Regulates Fat Storage","volume":"101","author":"Ding","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00281-013-0404-6","article-title":"Microbiota and Nonalcoholic Steatohepatitis","volume":"36","author":"Imajo","year":"2014","journal-title":"Semin. Immunopathol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Milosevic, I., Vujovic, A., Barac, A., Djelic, M., Korac, M., Radovanovic Spurnic, A., Gmizic, I., Stevanovic, O., Djordjevic, V., and Lekic, N. (2019). Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020395"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The Gut-Liver Axis in Liver Disease: Pathophysiological Basis for Therapy","volume":"72","author":"Albillos","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1053\/j.gastro.2019.12.054","article-title":"Adipose Tissue-Liver Cross Talk in the Control of Whole-Body Metabolism: Implications in Nonalcoholic Fatty Liver Disease","volume":"158","author":"Azzu","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1152\/physiol.00014.2014","article-title":"The Gut-Adipose-Liver Axis in the Metabolic Syndrome","volume":"29","author":"Konrad","year":"2014","journal-title":"Physiology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"329","DOI":"10.14218\/JCTH.2021.00178","article-title":"Metabolic-Associated Fatty Liver Disease (MAFLD): A Multi-Systemic Disease Beyond the Liver","volume":"10","author":"Kaya","year":"2022","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3389\/fcell.2014.00006","article-title":"Olfactomedin Proteins: Central Players in Development and Disease","volume":"2","author":"Anholt","year":"2014","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s12035-009-8076-x","article-title":"Olfactomedin Domain-Containing Proteins: Possible Mechanisms of Action and Functions in Normal Development and Pathology","volume":"40","author":"Tomarev","year":"2009","journal-title":"Mol. Neurobiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1074\/mcp.M113.035600","article-title":"Analysis of the Human Tissue-Specific Expression by Genome-Wide Integration of Transcriptomics and Antibody-Based Proteomics","volume":"13","author":"Fagerberg","year":"2014","journal-title":"Mol. Cell. Proteomics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17071","DOI":"10.1073\/pnas.1907308116","article-title":"BCL6 Regulates Brown Adipocyte Dormancy to Maintain Thermogenic Reserve and Fitness","volume":"116","author":"Kutyavin","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"155122","DOI":"10.1016\/j.metabol.2021.155122","article-title":"Olfactomedin 2 Deficiency Protects against Diet-Induced Obesity","volume":"129","author":"Nakaya","year":"2022","journal-title":"Metabolism"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0378-1119(01)00763-6","article-title":"Identification and Characterization of a Novel Member of Olfactomedin-Related Protein Family, HGC-1, Expressed during Myeloid Lineage Development","volume":"283","author":"Zhang","year":"2002","journal-title":"Gene"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1016\/j.yexcr.2006.02.011","article-title":"The Glycoprotein HGC-1 Binds to Cadherin and Lectins","volume":"312","author":"Liu","year":"2006","journal-title":"Exp. Cell Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s10555-016-9624-2","article-title":"Olfactomedin 4 Expression and Functions in Innate Immunity, Inflammation, and Cancer","volume":"35","author":"Liu","year":"2016","journal-title":"Cancer Metastasis Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5237","DOI":"10.1038\/onc.2016.58","article-title":"Olfactomedin 4 Deletion Induces Colon Adenocarcinoma in ApcMin\/+ Mice","volume":"35","author":"Liu","year":"2016","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bertran, L., Portillo-Carrasquer, M., Aguilar, C., Porras, J.A., Riesco, D., Mart\u00ednez, S., Vives, M., Sabench, F., Gonzalez, E., and Del Castillo, D. (2021). Deregulation of Secreted Frizzled-Related Protein 5 in Nonalcoholic Fatty Liver Disease Associated with Obesity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136895"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1002\/oby.22873","article-title":"Hepatocyte Notch Signaling Deregulation Related to Lipid Metabolism in Women with Obesity and Nonalcoholic Fatty Liver","volume":"28","author":"Auguet","year":"2020","journal-title":"Obesity"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1242\/dev.070763","article-title":"Notch Signaling Modulates Proliferation and Differentiation of Intestinal Crypt Base Columnar Stem Cells","volume":"139","author":"VanDussen","year":"2012","journal-title":"Development"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Tian, Y., Mok, M., Yang, P., and Cheng, A. (2016). Epigenetic Activation of Wnt\/\u03b2-Catenin Signaling in NAFLD-Associated Hepatocarcinogenesis. Cancers, 8.","DOI":"10.3390\/cancers8080076"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"792667","DOI":"10.3389\/fmolb.2021.792667","article-title":"The Role of Notch Signaling Pathway in Non-Alcoholic Fatty Liver Disease","volume":"8","author":"Xu","year":"2021","journal-title":"Front. Mol. Biosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"100714","DOI":"10.1016\/j.jbc.2021.100714","article-title":"NF-\u039aB P65 Regulates Hepatic Lipogenesis by Promoting Nuclear Entry of ChREBP in Response to a High Carbohydrate Diet","volume":"296","author":"Daniel","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11056","DOI":"10.1073\/pnas.1001269107","article-title":"Olfactomedin 4 Down-Regulates Innate Immunity against Helicobacter Pylori Infection","volume":"107","author":"Liu","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.3748\/wjg.v24.i17.1881","article-title":"Olfactomedin-4 in Digestive Diseases: A Mini-Review","volume":"24","author":"Wang","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.1365-2559.2007.02763.x","article-title":"Expression of HGC-1 Is Correlated with Differentiation of Gastric Carcinoma","volume":"51","author":"Liu","year":"2007","journal-title":"Histopathology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s10555-010-9262-z","article-title":"Stem Cell Marker Olfactomedin 4: Critical Appraisal of Its Characteristics and Role in Tumorigenesis","volume":"29","author":"Grover","year":"2010","journal-title":"Cancer Metastasis Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41575-018-0009-6","article-title":"Triggering and Resolution of Inflammation in NASH","volume":"15","author":"Schuster","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"718710","DOI":"10.3389\/fnut.2022.718710","article-title":"The Influence of Nutrition on Intestinal Permeability and the Microbiome in Health and Disease","volume":"9","author":"Inczefi","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"110885","DOI":"10.1016\/j.nut.2020.110885","article-title":"Intestinal Expression of Toll-like Receptor Gene Changes Early after Gastric Bypass Surgery and Association with Type 2 Diabetes Remission","volume":"79\u201380","author":"Sala","year":"2020","journal-title":"Nutrition"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"(2009). Enjoji Impact of Cholesterol Metabolism and the LXR\u03b1-SREBP-1c Pathway on Nonalcoholic Fatty Liver Disease. Int. J. Mol. Med., 23, 603\u2013608.","DOI":"10.3892\/ijmm_00000170"},{"key":"ref_39","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_40","doi-asserted-by":"crossref","first-page":"100346","DOI":"10.1016\/j.jhepr.2021.100346","article-title":"New Targets for NAFLD","volume":"3","author":"Parlati","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"22173","DOI":"10.3390\/ijms151222173","article-title":"Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease","volume":"15","author":"Auguet","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/s41366-019-0430-0","article-title":"Circulating Microbiota-Derived Metabolites: A \u201cliquid Biopsy?","volume":"44","author":"Aguilar","year":"2020","journal-title":"Int. J. Obes."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100479","DOI":"10.1016\/j.jhepr.2022.100479","article-title":"Lipid Alterations in Chronic Liver Disease and Liver Cancer","volume":"4","author":"Paul","year":"2022","journal-title":"JHEP Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD Development and Therapeutic Strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"19076","DOI":"10.1038\/srep19076","article-title":"Associations of Gut-Flora-Dependent Metabolite Trimethylamine-N-Oxide, Betaine and Choline with Non-Alcoholic Fatty Liver Disease in Adults","volume":"6","author":"Chen","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.jbiosc.2014.03.001","article-title":"Dietary Trimethylamine N-Oxide Exacerbates Impaired Glucose Tolerance in Mice Fed a High Fat Diet","volume":"118","author":"Gao","year":"2014","journal-title":"J. Biosci. Bioeng."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1900257","DOI":"10.1002\/mnfr.201900257","article-title":"Trimethylamine N-Oxide Aggravates Liver Steatosis through Modulation of Bile Acid Metabolism and Inhibition of Farnesoid X Receptor Signaling in Nonalcoholic Fatty Liver Disease","volume":"63","author":"Tan","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"40","DOI":"10.35454\/rncm.v4n4.287","article-title":"Relaci\u00f3n Entre Los \u00c1cidos Biliares y La Microbiota Intestinal \u00bfes Posible Considerarlo Como Un Factor Etiol\u00f3gico En Diversas Colangiopat\u00edas? Una Revisi\u00f3n Narrativa","volume":"4","author":"Waitzberg","year":"2021","journal-title":"Rev. Nutr. Cl\u00ednica Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"100222","DOI":"10.1016\/j.jhepr.2020.100222","article-title":"NASH-Related Increases in Plasma Bile Acid Levels Depend on Insulin Resistance","volume":"3","author":"Grzych","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"7381","DOI":"10.3748\/wjg.v20.i23.7381","article-title":"Role of Gut Microbiota and Toll-like Receptors in Nonalcoholic Fatty Liver Disease","volume":"20","author":"Miura","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s11154-020-09571-8","article-title":"Diet Approach before and after Bariatric Surgery","volume":"21","author":"Bettini","year":"2020","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1186\/s12967-019-2104-z","article-title":"The Management of Very Low-Calorie Ketogenic Diet in Obesity Outpatient Clinic: A Practical Guide","volume":"17","author":"Muscogiuri","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Rogero, M., and Calder, P. (2018). Obesity, Inflammation, Toll-Like Receptor 4 and Fatty Acids. Nutrients, 10.","DOI":"10.3390\/nu10040432"},{"key":"ref_54","first-page":"1353","article-title":"Novel Role of TLR4 in NAFLD Development: Modulation of Metabolic Enzymes Expression","volume":"1851","author":"Ferreira","year":"2015","journal-title":"Biochim. Biophys. Acta BBA Mol. Cell Biol. Lipids"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Zhang, W., Hartmann, R., Tun, H.M., Elson, C.O., Khafipour, E., and Garvey, W.T. (2016). Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150943"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.jcmgh.2016.04.007","article-title":"Hepatocyte Toll-Like Receptor 5 Promotes Bacterial Clearance and Protects Mice Against High-Fat Diet\u2013Induced Liver Disease","volume":"2","author":"Gewirtz","year":"2016","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1053\/j.gastro.2014.08.033","article-title":"Intestinal Epithelial Cell Toll-like Receptor 5 Regulates the Intestinal Microbiota to Prevent Low-Grade Inflammation and Metabolic Syndrome in Mice","volume":"147","author":"Chassaing","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_58","first-page":"16","article-title":"Toll-like Receptor 5-Mediated Signaling Enhances Liver Regeneration in Mice","volume":"8","author":"Zhang","year":"2021","journal-title":"Mil. Med. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1126\/science.1179721","article-title":"Metabolic Syndrome and Altered Gut Microbiota in Mice Lacking Toll-Like Receptor 5","volume":"328","author":"Aitken","year":"2010","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1002\/hep4.1237","article-title":"Serum Interleukin-8, Osteopontin, and Monocyte Chemoattractant Protein 1 Are Associated With Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease","volume":"2","author":"Glass","year":"2018","journal-title":"Hepatol. Commun."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"102429","DOI":"10.1016\/j.autrev.2019.102429","article-title":"Critical Role of Interleukin (IL)-17 in Inflammatory and Immune Disorders: An Updated Review of the Evidence Focusing in Controversies","volume":"19","author":"Puig","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ccell.2016.05.020","article-title":"Metabolic Inflammation-Associated IL-17A Causes Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma","volume":"30","author":"Gomes","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1111\/j.1365-2141.2008.07368.x","article-title":"The Regulation of OLFM4 Expression in Myeloid Precursor Cells Relies on NF-\u039aB Transcription Factor","volume":"143","author":"Chin","year":"2008","journal-title":"Br. J. Haematol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/978-3-319-48382-5_9","article-title":"The Pathogenesis of Obesity-Associated Adipose Tissue Inflammation","volume":"Volume 960","author":"Engin","year":"2017","journal-title":"Obesity and Lipotoxicity"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5771","DOI":"10.4049\/jimmunol.180.9.5771","article-title":"IL-10: The Master Regulator of Immunity to Infection","volume":"180","author":"Couper","year":"2008","journal-title":"J. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.jhep.2007.12.017","article-title":"Interleukin-10 Is a Protective Factor against Diet-Induced Insulin Resistance in Liver","volume":"48","author":"Cintra","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1210\/jc.2002-021437","article-title":"Association of Low Interleukin-10 Levels with the Metabolic Syndrome in Obese Women","volume":"88","author":"Esposito","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1161\/hh0901.090440","article-title":"Anti-Inflammatory Mechanisms in the Vascular Wall","volume":"88","author":"Tedgui","year":"2001","journal-title":"Circ. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"613639","DOI":"10.3389\/fendo.2020.613639","article-title":"TLR9 in MAFLD and NASH: At the Intersection of Inflammation and Metabolism","volume":"11","author":"Shepard","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1002\/hep.30645","article-title":"MicroRNA-223 Ameliorates Nonalcoholic Steatohepatitis and Cancer by Targeting Multiple Inflammatory and Oncogenic Genes in Hepatocytes","volume":"70","author":"He","year":"2019","journal-title":"Hepatology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and Validation of a Histological Scoring System for Nonalcoholic Fatty Liver Disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1111\/j.1572-0241.1999.01377.x","article-title":"Nonalcoholic Steatohepatitis: A Proposal for Grading and Staging The Histological Lesions","volume":"94","author":"Brunt","year":"1999","journal-title":"Am. J. Gastroenterol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7442\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:42:40Z","timestamp":1760139760000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/13\/7442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,4]]},"references-count":72,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["ijms23137442"],"URL":"https:\/\/doi.org\/10.3390\/ijms23137442","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,4]]}}}