{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:24:48Z","timestamp":1780957488863,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sapienza University of Rome \u201cAteneo 2019\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Lipopolysaccharide (LPS) and its binding protein LBP have emerged as potential contributors to the progression from overweight\/obesity to overt metabolic diseases and NAFLD. While LPS is known to activate hepatocyte inflammation, thus contributing toward NAFLD development, the role of LBP is more intricate, and recent data have shown that experimental reduction in hepatic LBP promotes NAFLD progression. In this cross-sectional investigation, we evaluated circulating LBP in relation to obesity, NAFLD, visceral adipose tissue (VAT) inflammation, and type 2 diabetes (T2D). We recruited 186 individuals (M\/F: 81\/105; age: 47 \u00b1 10.4 years; BMI: 35.5 \u00b1 8.6 kg\/m2); a subgroup (n = 81) underwent bariatric surgery with intra-operative VAT and liver biopsies. LBP levels were higher in obese individuals than non-obese individuals but were inversely correlated with the parameters of glucose metabolism. Reduced LBP predicted T2D independent of age, sex, and BMI (p &lt; 0.001). LBP levels decreased across more severe stages of hepatosteatosis and lobular inflammation, and were inversely associated with VAT inflammation signatures. In conclusion, LBP levels are increased in obese individuals and are associated with a more favorable metabolic profile and lower NAFLD\/NASH prevalence. A possible explanation for these findings is that hepatic LBP production may be triggered by chronic caloric excess and facilitate LPS degradation in the liver, thus protecting these individuals from the metabolic consequences of obesity.<\/jats:p>","DOI":"10.3390\/ijms242417174","type":"journal-article","created":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T03:48:41Z","timestamp":1701834521000},"page":"17174","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Reduced Lipopolysaccharide-Binding Protein (LBP) Levels Are Associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and Adipose Inflammation in Human Obesity"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0530-8568","authenticated-orcid":false,"given":"Ilaria","family":"Barchetta","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia Agata","family":"Cimini","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Sentinelli","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Chiappetta","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2891-5598","authenticated-orcid":false,"given":"Claudio","family":"Di Cristofano","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Silecchia","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Translational Medicine, Faculty of Medicine and Psychology, St Andrea Hospital, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frida","family":"Leonetti","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, 04100 Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3224-6078","authenticated-orcid":false,"given":"Marco Giorgio","family":"Baroni","sequence":"additional","affiliation":[{"name":"Endocrinology and Diabetes, Department of Clinical Medicine, Public Health, Life and Environmental Sciences (MeSVA), University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"},{"name":"Neuroendocrinology and Metabolic Diseases, IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6630-8049","authenticated-orcid":false,"given":"Maria Gisella","family":"Cavallo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.3350\/cmh.2022.0365","article-title":"Global incidence and prevalence of nonalcoholic fatty liver disease","volume":"29","author":"Teng","year":"2023","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cmet.2017.08.002","article-title":"Nonalcoholic fatty liver disease as a nexus of metabolic and hepatic diseases","volume":"27","author":"Samuel","year":"2018","journal-title":"Cell Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/j.jhep.2023.06.003","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"79","author":"Rinella","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S2213-8587(22)00003-1","article-title":"A global view of the interplay between nonalcoholic fatty liver disease and diabetes","volume":"10","author":"Stefan","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1097\/HEP.0000000000000323","article-title":"AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease","volume":"77","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1210\/endrev\/bnac004","article-title":"The Metabolic Role and Therapeutic Potential of the Microbiome","volume":"43","author":"Olofsson","year":"2022","journal-title":"Endocr. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1039\/D2FO02463B","article-title":"Orally administered octacosanol improves liver insulin resistance in high-fat diet-fed mice through the reconstruction of the gut microbiota structure and inhibition of the TLR4\/NF-kappaB inflammatory pathway","volume":"14","author":"Ding","year":"2023","journal-title":"Food Funct."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.jcmgh.2023.09.002","article-title":"DNMT3B Alleviates Liver Steatosis Induced by Chronic Low-grade LPS via Inhibiting CIDEA Expression","volume":"17","author":"Li","year":"2024","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0171-2985(11)80341-4","article-title":"Lipopolysaccharide binding protein and CD14 in LPS-dependent macrophage activation","volume":"187","author":"Tobias","year":"1993","journal-title":"Immunobiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1126\/science.2402637","article-title":"Structure and function of lipopolysaccharide binding protein","volume":"249","author":"Schumann","year":"1990","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1194\/jlr.M200440-JLR200","article-title":"A single intravenous dose of endotoxin rapidly alters serum lipoproteins and lipid transfer proteins in normal volunteers","volume":"44","author":"Hudgins","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S1471-4906(02)02233-0","article-title":"Lipopolysaccharide recognition: CD14, TLRs, and the LPS-activation cluster","volume":"23","author":"Triantafilou","year":"2002","journal-title":"Trends Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Gonzalez-Quintela, A., Alonso, M., Campos, J., Vizcaino, L., Loidi, L., and Gude, F. (2013). Determinants of serum concentrations of lipopolysaccharide-binding protein (LBP) in the adult population: The role of obesity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054600"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3345\/kjp.2016.59.5.231","article-title":"Lipopolysaccharide-binding protein plasma levels as a biomarker of obesity-related insulin resistance in adolescents","volume":"59","author":"Kim","year":"2016","journal-title":"Korean J. Pediatr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.atherosclerosis.2013.07.004","article-title":"Serum lipopolysaccharide-binding protein as a marker of atherosclerosis","volume":"230","author":"Serrano","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e12946","DOI":"10.1111\/ijpo.12946","article-title":"Serum zonulin as an index of glucose dysregulation in children and adolescents with overweight and obesity","volume":"17","author":"Olivieri","year":"2022","journal-title":"Pediatr. Obes."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.numecd.2022.09.026","article-title":"Putative intestinal permeability markers do not correlate with cardiometabolic health and gut microbiota in humans, except for peptides recognized by a widely used zonulin ELISA kit","volume":"33","author":"Rivera","year":"2023","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e3018","DOI":"10.1210\/clinem\/dgac149","article-title":"Endotoxin Biomarkers Are Associated with Adiposity and Cardiometabolic Risk across 6 Years of Follow-up in Youth","volume":"107","author":"Perng","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1007\/s40520-020-01684-z","article-title":"Lipopolysaccharide binding protein is associated with CVD risk in older adults","volume":"33","author":"Roberts","year":"2021","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"106562","DOI":"10.1016\/j.phrs.2022.106562","article-title":"Liver lipopolysaccharide binding protein prevents hepatic inflammation in physiological and pathological non-obesogenic conditions","volume":"187","author":"Milbank","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kessoku, T., Kobayashi, T., Tanaka, K., Yamamoto, A., Takahashi, K., Iwaki, M., Ozaki, A., Kasai, Y., Nogami, A., and Honda, Y. (2021). The Role of Leaky Gut in Nonalcoholic Fatty Liver Disease: A Novel Therapeutic Target. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158161"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.jacc.2007.02.070","article-title":"Association of lipopolysaccharide-binding protein and coronary artery disease in men","volume":"50","author":"Lepper","year":"2007","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2337\/dc15-1777","article-title":"Association of Lipopolysaccharide-Binding Protein with Aging-Related Adiposity Change and Prediabetes among African Ancestry Men","volume":"39","author":"Tilves","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/1753-0407.12281","article-title":"Lipopolysaccharide-binding protein cannot independently predict type 2 diabetes mellitus: A nested case-control study","volume":"8","author":"Zhou","year":"2016","journal-title":"J. Diabetes"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ojo, O., Ojo, O.O., Zand, N., and Wang, X. (2021). The Effect of Dietary Fiber on Gut Microbiota, Lipid Profile, and Inflammatory Markers in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients, 13.","DOI":"10.3390\/nu13061805"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Tamaki, S., Kanazawa, A., Sato, J., Tamura, Y., Asahara, T., Takahashi, T., Matsumoto, S., Yamashiro, Y., and Watada, H. (2019). Clinical factors associated with bacterial translocation in Japanese patients with type 2 diabetes: A retrospective study. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222598"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9680","DOI":"10.1038\/s41598-017-09860-4","article-title":"Lipopolysaccharide-binding protein (LBP) reverses the amyloid state of fibrin seen in plasma of type 2 diabetics with cardiovascular co-morbidities","volume":"7","author":"Pretorius","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"eabe6729","DOI":"10.1126\/science.abe6729","article-title":"Enterically derived high-density lipoprotein restrains liver injury through the portal vein","volume":"373","author":"Han","year":"2021","journal-title":"Science"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1084\/jem.180.3.1025","article-title":"Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS","volume":"180","author":"Wurfel","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e3358","DOI":"10.1002\/dmrr.3358","article-title":"Adipose tissue remodelling in obese subjects is a determinant of presence and severity of fatty liver disease","volume":"37","author":"Cimini","year":"2021","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Barchetta, I., Cimini, F.A., Capoccia, D., Bertoccini, L., Ceccarelli, V., Chiappetta, C., Leonetti, F., Di Cristofano, C., Silecchia, G., and Orho-Melander, M. (2018). Neurotensin Is a Lipid-Induced Gastrointestinal Peptide Associated with Visceral Adipose Tissue Inflammation in Obesity. Nutrients, 10.","DOI":"10.3390\/nu10040526"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1210\/jc.2017-02751","article-title":"Increased Plasma Proneurotensin Levels Identify NAFLD in Adults with and without Type 2 Diabetes","volume":"103","author":"Barchetta","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.2337\/dc23-S002","article-title":"2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes-2023","volume":"46","author":"ElSayed","year":"2023","journal-title":"Diabetes Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1002\/hep.22742","article-title":"Liver biopsy","volume":"49","author":"Rockey","year":"2009","journal-title":"Hepatology"},{"key":"ref_37","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."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Barchetta, I., Chiappetta, C., Ceccarelli, V., Cimini, F.A., Bertoccini, L., Gaggini, M., Cristofano, D., Silecchia, G., Lenzi, A., and Leonetti, F. (2020). Angiopoietin-like Protein 4 Overexpression in Visceral Adipose Tissue from Obese Subjects with Impaired Glucose Metabolism and Relationship with Lipoprotein Lipase. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197197"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17174\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:33:52Z","timestamp":1760132032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17174"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,6]]},"references-count":38,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242417174"],"URL":"https:\/\/doi.org\/10.3390\/ijms242417174","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,6]]}}}