{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T03:51:18Z","timestamp":1785297078574,"version":"3.55.0"},"reference-count":59,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T00:00:00Z","timestamp":1696204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austral University","award":["T-14"],"award-info":[{"award-number":["T-14"]}]},{"name":"Austral University","award":["T-13"],"award-info":[{"award-number":["T-13"]}]},{"name":"Austral University","award":["PICT 2018\/03097"],"award-info":[{"award-number":["PICT 2018\/03097"]}]},{"name":"Austral University","award":["PICT 2018\/4053"],"award-info":[{"award-number":["PICT 2018\/4053"]}]},{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica (ANPCyT)","award":["T-14"],"award-info":[{"award-number":["T-14"]}]},{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica (ANPCyT)","award":["T-13"],"award-info":[{"award-number":["T-13"]}]},{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica (ANPCyT)","award":["PICT 2018\/03097"],"award-info":[{"award-number":["PICT 2018\/03097"]}]},{"name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica (ANPCyT)","award":["PICT 2018\/4053"],"award-info":[{"award-number":["PICT 2018\/4053"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The severity of non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to steatohepatitis, and it is not yet clearly understood which patients will progress to liver fibrosis or cirrhosis. SPARC (Secreted Protein Acidic and Rich in Cysteine) has been involved in NAFLD pathogenesis in mice and humans. The aim of this study was to investigate the role of SPARC in inflammasome activation, and to evaluate the relationship between the hepatic expression of inflammasome genes and the biochemical and histological characteristics of NAFLD in obese patients. In vitro studies were conducted in a macrophage cell line and primary hepatocyte cultures to assess the effect of SPARC on inflammasome. A NAFLD model was established in SPARC knockout (SPARC\u2212\/\u2212) and SPARC+\/+ mice to explore inflammasome activation. A hepatic RNAseq database from NAFLD patients was analyzed to identify genes associated with SPARC expression. The results were validated in a prospective cohort of 59 morbidly obese patients with NAFLD undergoing bariatric surgery. Our results reveal that SPARC alone or in combination with saturated fatty acids promoted IL-1\u03b2 expression in cell cultures. SPARC\u2212\/\u2212 mice had reduced hepatic inflammasome activation during the progression of NAFLD. NAFLD patients showed increased expression of SPARC, NLRP3, CASP1, and IL-1\u03b2. Gene ontology analysis revealed that genes positively correlated with SPARC are linked to inflammasome-related pathways during the progression of the disease, enabling the differentiation of patients between steatosis and steatohepatitis. In conclusion, SPARC may play a role in hepatic inflammasome activation in NAFLD.<\/jats:p>","DOI":"10.3390\/ijms241914843","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T11:56:49Z","timestamp":1696247809000},"page":"14843","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hepatic SPARC Expression Is Associated with Inflammasome Activation during the Progression of Non-Alcoholic Fatty Liver Disease in Both Mice and Morbidly Obese Patients"],"prefix":"10.3390","volume":"24","author":[{"given":"Agostina M.","family":"Onorato","sequence":"first","affiliation":[{"name":"Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET-Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Lameroli Mauriz","sequence":"additional","affiliation":[{"name":"Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET-Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Bayo","sequence":"additional","affiliation":[{"name":"Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET-Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1059-1695","authenticated-orcid":false,"given":"Esteban","family":"Fiore","sequence":"additional","affiliation":[{"name":"Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET-Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Cantero","sequence":"additional","affiliation":[{"name":"Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET-Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-0910","authenticated-orcid":false,"given":"Barbara","family":"Bueloni","sequence":"additional","affiliation":[{"name":"Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET-Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8999-5347","authenticated-orcid":false,"given":"Mariana","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET-Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Lag\u00fces","sequence":"additional","affiliation":[{"name":"Pathological Anatomy Department, Hospital Universitario Austral, Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Mart\u00ednez-Duartez","sequence":"additional","affiliation":[{"name":"Bariatric and Metabolic Surgery Department, Hospital Universitario Austral, Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Menaldi","sequence":"additional","affiliation":[{"name":"Bariatric and Metabolic Surgery Department, Hospital Universitario Austral, Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Paleari","sequence":"additional","affiliation":[{"name":"Bariatric and Metabolic Surgery Department, Hospital Universitario Austral, Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Atorrasagasti","sequence":"additional","affiliation":[{"name":"Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET-Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo D.","family":"Mazzolini","sequence":"additional","affiliation":[{"name":"Gene Therapy Laboratory, Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biom\u00e9dicas, CONICET-Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"},{"name":"Liver Unit, Hospital Universitario Austral, Universidad Austral, Av. Pte. Per\u00f3n 1500, Pilar B1629AHJ, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1002\/hep.30251","article-title":"Global Perspectives on Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis","volume":"69","author":"Younossi","year":"2019","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1146\/annurev-pathol-012615-044224","article-title":"Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum","volume":"11","author":"Hardy","year":"2016","journal-title":"Annu. 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