{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:14:55Z","timestamp":1785420895486,"version":"3.56.0"},"reference-count":67,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2020-0691"],"award-info":[{"award-number":["PICT 2020-0691"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PICT 2020-0691"],"award-info":[{"award-number":["PICT 2020-0691"]}],"id":[{"id":"https:\/\/ror.org\/03stxzb56","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>The most common complication of active brucellosis in humans is osteoarticular injury. In the bone marrow microenvironment, mesenchymal stem cells (MSCs) can differentiate into either adipocytes or osteoblasts, and this balance is tightly regulated because an increase in adipogenesis may negatively affect bone formation and favor bone loss. The differentiation of MSCs into adipocytes or osteoblasts is tightly regulated by mechanisms that promote cell fate toward one lineage while repressing the other. Our study demonstrated that Brucella abortus infects MSCs but does not affect the deposition of organic and mineral matrix during osteoblast differentiation. However, the infection upregulates Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) expression in osteoblasts, which may contribute to osteoclast activation and bone resorption. Conversely, B. abortus infection significantly influences adipocyte differentiation by modulating lipolysis, lipogenesis, and interactions between lipid droplets and mitochondria. This leads to increased cellular cholesterol levels and reduced intracellular triglycerides, accompanied by glycerol release. These changes result in more differentiated adipocytes and larger lipid droplets. Consequently, we observed increased IL-6 secretion and a higher leptin\/adiponectin ratio. Importantly, these effects were independent of a functional type IV secretion system (T4SS), as purified Brucella DNA fully reproduced the adipogenic phenotype. Moreover, inhibition of TLR9\u2014the primary sensor of bacterial DNA\u2014significantly reduced the DNA-induced adipogenic response, demonstrating that adipocyte modulation is at least in part mediated through TLR9 signaling. In summary, B. abortus promotes MSC differentiation toward an inflammatory adipocyte phenotype. It involves a TLR-9-mediated DNA detection. It may contribute to osteoarticular injury and infection-associated bone resorption.<\/jats:p>","DOI":"10.3390\/tropicalmed11050112","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:09:12Z","timestamp":1776935352000},"page":"112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Brucella abortus Infection Promotes Mesenchymal Stem Cell Differentiation Toward Adipogenesis, Enhancing the Proinflammatory Profile"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7461-5687","authenticated-orcid":false,"given":"Rosa Nicole","family":"Freiberger","sequence":"first","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Laboratorio de Inmunopatolog\u00eda Viral, Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires (UBA), Buenos Aires 1121, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1603-9156","authenticated-orcid":false,"given":"Cynthia Alicia Marcela","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Laboratorio de Inmunopatolog\u00eda Viral, Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires (UBA), Buenos Aires 1121, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Bel\u00e9n","family":"Palma","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Citolog\u00eda, Histolog\u00eda y Embriolog\u00eda, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de La Plata, La Plata 1900, Argentina"},{"name":"Laboratorio de Investigaci\u00f3n Aplicada a Neurociencias (LIAN), Fleni, Consejo de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Escobar 1625, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9268-0853","authenticated-orcid":false,"given":"Cintia","family":"Cevallos","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Laboratorio de Inmunopatolog\u00eda Viral, Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires (UBA), Buenos Aires 1121, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco Agustin","family":"Sviercz","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Laboratorio de Inmunopatolog\u00eda Viral, Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires (UBA), Buenos Aires 1121, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2844-2873","authenticated-orcid":false,"given":"Patricio","family":"Jarmoluk","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Laboratorio de Inmunopatolog\u00eda Viral, Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires (UBA), Buenos Aires 1121, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3032-9467","authenticated-orcid":false,"given":"Marcela Nilda","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Citolog\u00eda, Histolog\u00eda y Embriolog\u00eda, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de La Plata, La Plata 1900, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5110-8773","authenticated-orcid":false,"given":"Jorge","family":"Quarleri","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y Tecnol\u00f3gicas (CONICET), Laboratorio de Inmunopatolog\u00eda Viral, Instituto de Investigaciones Biom\u00e9dicas en Retrovirus y Sida (INBIRS), Universidad de Buenos Aires (UBA), Buenos Aires 1121, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2077-8509","authenticated-orcid":false,"given":"M. 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Microbes Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.5312\/wjo.v10.i2.54","article-title":"Osteoarticular manifestations of human brucellosis: A review","volume":"10","year":"2019","journal-title":"World J. Orthop."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1097\/01.mnm.0000167651.52724.68","article-title":"Scintigraphic findings in osteoarticular brucellosis","volume":"26","author":"Aydin","year":"2005","journal-title":"Nucl. Med. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0049-0172(82)90064-6","article-title":"Articular involvement in human brucellosis: A retrospective analysis of 304 cases","volume":"12","author":"Gotuzzo","year":"1982","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1136\/ard.49.12.994","article-title":"Brucella arthritis: A study of 96 cases in Kuwait","volume":"49","author":"Khateeb","year":"1990","journal-title":"Ann. Rheum. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"873","DOI":"10.2214\/AJR.05.1088","article-title":"Epidemiologic, clinical, and imaging findings in brucellosis patients with osteoarticular involvement","volume":"187","author":"Pourbagher","year":"2006","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e469","DOI":"10.1016\/j.ijid.2009.06.031","article-title":"Clinical manifestations and complications in 1028 cases of brucellosis: A retrospective evaluation and review of the literature","volume":"14","author":"Buzgan","year":"2010","journal-title":"Int. J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Madkour, M.M. (2001). Osteoarticular brucellosis. Madkour\u2019s Brucellosis, Springer. [2nd ed.].","DOI":"10.1007\/978-3-642-59533-2"},{"key":"ref_9","first-page":"1871","article-title":"Bone marrow biopsy findings in brucellosis patients with hematologic abnormalities","volume":"125","author":"Demir","year":"2012","journal-title":"Chin. Med. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e2013011","DOI":"10.4084\/mjhid.2013.011","article-title":"A prospective study of brucellosis in children: Relative frequency of pancytopenia","volume":"5","author":"Afify","year":"2013","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/sj.bmt.1702480","article-title":"Brucellosis transmitted by bone marrow transplantation","volume":"26","author":"Ertem","year":"2000","journal-title":"Bone Marrow Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1146\/annurev-micro-090110-102905","article-title":"Interactions of the human pathogenic Brucella species with their hosts","volume":"65","author":"Atluri","year":"2011","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gonzalez-Espinoza, G., Arce-Gorvel, V., Memet, S., and Gorvel, J.P. (2021). Brucella: Reservoirs and Niches in Animals and Humans. Pathogens, 10.","DOI":"10.3390\/pathogens10020186"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/978-1-60761-999-4_19","article-title":"Adipogenic differentiation of human mesenchymal stem cells","volume":"698","author":"Fink","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1096\/fj.03-1100fje","article-title":"Transdifferentiation potential of human mesenchymal stem cells derived from bone marrow","volume":"18","author":"Song","year":"2004","journal-title":"FASEB J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s00018-013-1440-z","article-title":"Osteoblast-adipocyte lineage plasticity in tissue development, maintenance and pathology","volume":"71","author":"Berendsen","year":"2014","journal-title":"Cell Mol. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/ncprheum0070","article-title":"Mechanisms of disease: Is osteoporosis the obesity of bone?","volume":"2","author":"Rosen","year":"2006","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ali, D., Tencerova, M., Figeac, F., Kassem, M., and Jafari, A. (2022). The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.981487"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1136\/jcp.55.9.693","article-title":"Adipocytic proportion of bone marrow is inversely related to bone formation in osteoporosis","volume":"55","author":"Verma","year":"2002","journal-title":"J. Clin. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1474-9728.2004.00127.x","article-title":"Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma\/stem cells: The role of PPAR-gamma2 transcription factor and TGF-beta\/BMP signaling pathways","volume":"3","author":"Moerman","year":"2004","journal-title":"Aging Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/jmri.20367","article-title":"Osteoporosis is associated with increased marrow fat content and decreased marrow fat unsaturation: A proton MR spectroscopy study","volume":"22","author":"Yeung","year":"2005","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/jcb.20777","article-title":"Playing with bone and fat","volume":"98","author":"Gimble","year":"2006","journal-title":"J. Cell Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nrm2066","article-title":"Adipocyte differentiation from the inside out","volume":"7","author":"Rosen","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/978-1-4419-1050-9_5","article-title":"Regulation of osteoblast differentiation by Runx2","volume":"658","author":"Komori","year":"2010","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"23270","DOI":"10.1074\/jbc.M211610200","article-title":"Activation of peroxisome proliferator-activated receptor-gamma inhibits the Runx2-mediated transcription of osteocalcin in osteoblasts","volume":"278","author":"Jeon","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Freiberger, R.N., Lopez, C.A.M., Sviercz, F.A., Cevallos, C., Guano, A.D., Jarmoluk, P., Quarleri, J., and Delpino, M.V.B. (2023). abortus Infection Promotes an Imbalance in the Adipocyte-Osteoblast Crosstalk Favoring Bone Resorption. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065617"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1128\/IAI.00208-12","article-title":"Brucella abortus invasion of osteoblasts inhibits bone formation","volume":"80","author":"Scian","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Pesce Viglietti, A.I., Giambartolomei, G.H., Quarleri, J., and Delpino, M.V. (2020). Brucella abortus Infection Modulates 3T3-L1 Adipocyte Inflammatory Response and Inhibits Adipogenesis. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.585923"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1128\/IAI.01259-08","article-title":"Proinflammatory response of human osteoblastic cell lines and osteoblast-monocyte interaction upon infection with Brucella spp","volume":"77","author":"Delpino","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"963689721993774","DOI":"10.1177\/0963689721993774","article-title":"Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells","volume":"30","author":"Palma","year":"2021","journal-title":"Cell Transplant."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Xiao, B., Deng, X., Zhou, W., and Tan, E.K. (2016). Flow Cytometry-Based Assessment of Mitophagy Using MitoTracker. Front. Cell Neurosci., 10.","DOI":"10.3389\/fncel.2016.00076"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1111\/j.1365-2818.1993.tb03313.x","article-title":"Measurement of co-localization of objects in dual-colour confocal images","volume":"169","author":"Manders","year":"1993","journal-title":"J. Microsc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/196987a0","article-title":"A rapid enzymatic assay for glycerol","volume":"196","author":"Garland","year":"1962","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s11914-012-0103-6","article-title":"Effects of bone matrix proteins on fracture and fragility in osteoporosis","volume":"10","author":"Sroga","year":"2012","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s00774-020-01175-1","article-title":"Discovery of the RANKL\/RANK\/OPG system","volume":"39","author":"Yasuda","year":"2021","journal-title":"J. Bone Miner. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.cell.2021.12.016","article-title":"Adipose-tissue plasticity in health and disease","volume":"185","author":"Sakers","year":"2022","journal-title":"Cell"},{"key":"ref_37","first-page":"435","article-title":"Lipid Droplets and the Management of Cellular Stress","volume":"92","author":"Jarc","year":"2019","journal-title":"Yale J. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.cmet.2019.02.011","article-title":"Mitochondria Bound to Lipid Droplets: Where Mitochondrial Dynamics Regulate Lipid Storage and Utilization","volume":"29","author":"Benador","year":"2019","journal-title":"Cell Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1046\/j.1462-5822.2001.00102.x","article-title":"Essential role of the VirB machinery in the maturation of the Brucella abortus-containing vacuole","volume":"3","author":"Comerci","year":"2001","journal-title":"Cell Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1128\/IAI.01227-15","article-title":"The Effector Protein BPE005 from Brucella abortus Induces Collagen Deposition and Matrix Metalloproteinase 9 Downmodulation via Transforming Growth Factor beta1 in Hepatic Stellate Cells","volume":"84","author":"Herrmann","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Arriola Benitez, P.C., Pesce Viglietti, A.I., Gomes, M.T.R., Oliveira, S.C., Quarleri, J.F., Giambartolomei, G.H., and Delpino, M.V. (2019). Brucella abortus Infection Elicited Hepatic Stellate Cell-Mediated Fibrosis Through Inflammasome-Dependent IL-1beta Production. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.03036"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"de Jong, M.F., Starr, T., Winter, M.G., den Hartigh, A.B., Child, R., Knodler, L.A., van Dijl, J.M., Celli, J., and Tsolis, R.M. (2013). Sensing of bacterial type IV secretion via the unfolded protein response. mBio, 4.","DOI":"10.1128\/mBio.00418-12"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1136\/gutjnl-2019-320118","article-title":"Adipose tissue derived bacteria are associated with inflammation in obesity and type 2 diabetes","volume":"69","author":"Massier","year":"2020","journal-title":"Gut"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, W., Yang, G., Liu, P., Jiang, X., and Xin, Y. (2022). Modulation of adipose tissue metabolism by microbial-derived metabolites. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.1031498"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.micinf.2014.08.010","article-title":"Brucella abortus DNA is a major bacterial agonist to activate the host innate immune system","volume":"16","author":"Campos","year":"2014","journal-title":"Microbes Infect."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cell.2007.10.004","article-title":"Developmental origin of fat: Tracking obesity to its source","volume":"131","author":"Gesta","year":"2007","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13578-019-0281-3","article-title":"Comparison of osteogenic differentiation capacity in mesenchymal stem cells derived from human amniotic membrane (AM), umbilical cord (UC), chorionic membrane (CM), and decidua (DC)","volume":"9","author":"Shen","year":"2019","journal-title":"Cell Biosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1007\/s00264-013-2059-2","article-title":"Role of mesenchymal stem cells in bone regeneration and fracture repair: A review","volume":"37","author":"Wang","year":"2013","journal-title":"Int. Orthop."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/s41392-023-01467-8","article-title":"Targeting strategies for bone diseases: Signaling pathways and clinical studies","volume":"8","author":"Xu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_50","first-page":"123","article-title":"Role of RANKL-RANK\/osteoprotegerin pathway in cardiovascular and bone disease associated with HIV infection","volume":"16","author":"Kelesidis","year":"2014","journal-title":"AIDS Rev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3402\/jom.v2i0.5532","article-title":"Role of periodontal pathogenic bacteria in RANKL-mediated bone destruction in periodontal disease","volume":"2","author":"Kajiya","year":"2010","journal-title":"J. Oral. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6040","DOI":"10.1073\/pnas.1318859111","article-title":"Arthritogenic alphaviral infection perturbs osteoblast function and triggers pathologic bone loss","volume":"111","author":"Chen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Granata, V., Possetti, V., Parente, R., Bottazzi, B., Inforzato, A., and Sobacchi, C. (2022). The osteoblast secretome in Staphylococcus aureus osteomyelitis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1048505"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"30057","DOI":"10.1074\/jbc.273.46.30057","article-title":"The role of C\/EBP genes in adipocyte differentiation","volume":"273","author":"Darlington","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"21005","DOI":"10.1074\/jbc.M702871200","article-title":"Sequential regulation of diacylglycerol acyltransferase 2 expression by CAAT\/enhancer-binding protein beta (C\/EBPbeta) and C\/EBPalpha during adipogenesis","volume":"282","author":"Payne","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0092-8674(05)80095-9","article-title":"SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene","volume":"75","author":"Yokoyama","year":"1993","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0092-8674(00)80213-5","article-title":"The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor","volume":"89","author":"Brown","year":"1997","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"11603","DOI":"10.1073\/pnas.90.24.11603","article-title":"SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element","volume":"90","author":"Hua","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"E2045","DOI":"10.1210\/jc.2011-1702","article-title":"Regulation of lipolysis in small and large fat cells of the same subject","volume":"96","author":"Laurencikiene","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10993","DOI":"10.1073\/pnas.0503291102","article-title":"Aquaporin 7 deficiency is associated with development of obesity through activation of adipose glycerol kinase","volume":"102","author":"Hibuse","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"29164","DOI":"10.1074\/jbc.273.44.29164","article-title":"Obesity-related overexpression of fatty-acid synthase gene in adipose tissue involves sterol regulatory element-binding protein transcription factors","volume":"273","author":"Boizard","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/27376","article-title":"Leptin and the regulation of body weight in mammals","volume":"395","author":"Friedman","year":"1998","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.cyto.2018.06.034","article-title":"Interleukin-6 as a \u201cmetabolic hormone\u201d","volume":"112","author":"Ghanemi","year":"2018","journal-title":"Cytokine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3629","DOI":"10.4049\/jimmunol.1202817","article-title":"Critical role of ASC inflammasomes and bacterial type IV secretion system in caspase-1 activation and host innate resistance to Brucella abortus infection","volume":"190","author":"Gomes","year":"2013","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1111\/j.1462-5822.2007.00922.x","article-title":"Brucella requires a functional Type IV secretion system to elicit innate immune responses in mice","volume":"9","author":"Roux","year":"2007","journal-title":"Cell Microbiol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Gomes, M.T., Campos, P.C., de Almeida, L.A., Oliveira, F.S., Costa, M.M., Marim, F.M., Pereira, G.S., and Oliveira, S.C. (2012). The role of innate immune signals in immunity to Brucella abortus. Front. Cell Infect. Microbiol., 2.","DOI":"10.3389\/fcimb.2012.00130"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"32","DOI":"10.51585\/gjvr.2024.1.0072","article-title":"Exploring in vivo and in vitro infection models in brucellosis research: A mini-review","volume":"4","author":"Jamil","year":"2024","journal-title":"Ger. J. Vet. Res."}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/11\/5\/112\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:35:45Z","timestamp":1776936945000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/11\/5\/112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":67,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["tropicalmed11050112"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed11050112","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]}}}