Meta-inflammation and de novo lipogenesis markers are involved in metabolic associated fatty liver disease progression in BTBR ob/ob mice

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• dc.contributor.author Opazo Ríos, Lucas
• dc.contributor.author Soto-Catalán, Manuel
• dc.contributor.author Lázaro, Iolanda
• dc.contributor.author Sala Vila, Aleix
• dc.contributor.author Jiménez-Castilla, Luna
• dc.contributor.author Orejudo, Macarena
• dc.contributor.author Moreno Bravo, Juan Antonio
• dc.contributor.author Egido, Jesús (Egido de los Ríos)
• dc.contributor.author Mas Fontao, Sebastián
• dc.date.accessioned 2022-09-27T06:06:56Z
• dc.date.available 2022-09-27T06:06:56Z
• dc.date.issued 2022
• dc.description.abstract Metabolic associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome and usually associated with obesity and diabetes. Our aim is to characterize the pathophysiological mechanism involved in MAFLD development in Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob). We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4-22 weeks. Lipid composition was assessed, and lipid related pathways were studied at transcriptional and protein level. Microvesicular steatosis was evident in BTBR ob/ob from week 6, progressing to macrovesicular in the following weeks. At 12th week, inflammatory clusters, activation of STAT3 and Nrf2 signaling pathways, and hepatocellular ballooning. At 22 weeks, the histopathological features previously observed were maintained and no signs of fibrosis were detected. Lipidomic analysis showed profiles associated with de novo lipogenesis (DNL). BTBR ob/ob mice develop MAFLD profile that resemble pathological features observed in humans, with overactivation of inflammatory response, oxidative stress and DNL signaling pathways. Therefore, BTBR ob/ob mouse is an excellent model for the study of the steatosis to steatohepatitis transition.
• dc.format.mimetype application/pdf
• dc.identifier.citation Opazo-Ríos L, Soto-Catalán M, Lázaro I, Sala-Vila A, Jiménez-Castilla L, Orejudo M, Moreno JA, Egido J, Mas-Fontao S. Meta-inflammation and de novo lipogenesis markers are involved in metabolic associated fatty liver disease progression in BTBR ob/ob mice. Int J Mol Sci. 2022 Apr 2;23(7):3965. DOI: 10.3390/ijms23073965
• dc.identifier.doi http://dx.doi.org/10.3390/ijms23073965
• dc.identifier.issn 1422-0067
• dc.identifier.uri http://hdl.handle.net/10230/54173
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Int J Mol Sci. 2022 Apr 2;23(7):3965
• dc.rights © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword BTBR ob/ob
• dc.subject.keyword De novo lipogenesis
• dc.subject.keyword Meta-inflammation
• dc.subject.keyword Metabolic associated fatty liver disease
• dc.title Meta-inflammation and de novo lipogenesis markers are involved in metabolic associated fatty liver disease progression in BTBR ob/ob mice
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion