Imaging and immunometabolic phenotyping uncover changes in the hepatic immune response in the early phases of NAFLD

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dc.creatorAriane Barros Diniz
dc.creatorMaísa Mota Antunes
dc.creatorViviane Aparecida de Souza Lacerda
dc.creatorBrenda Naemi Nakagak
dc.creatorMaria Alice Freitas Lopes
dc.creatorHortência Maciel de Castro-Oliveira
dc.creatorMatheus Silvério Mattos
dc.creatorKassiana Mafra Bicalho
dc.creatorCamila Dutra Moreira de Miranda
dc.creatorKaren Marques de Oliveira Costa
dc.creatorMateus Eustáquio de Moura Lopes
dc.creatorDébora Moreira Alvarenga
dc.creatorRaquel Carvalho-Gontijo
dc.creatorSarah Cozzer Marchesi
dc.creatorDebora Romualdo Lacerda
dc.creatorAlan Moreira de Araújo
dc.creatorÉrika de Carvalho
dc.creatorBruna Araújo David
dc.creatorMônica Morais Santos
dc.creatorCristiano Xavier Lima
dc.creatorJuliana Assis Silva Gomes
dc.creatorTereza Cristina Minto Fontes Cal
dc.creatorBruna Roque de Souza
dc.creatorCláudia Alves Couto
dc.creatorLuciana Costa Faria
dc.creatorPaula Vieira Teixeira Vidigal
dc.creatorAdaliene Versiane Matos Ferreira
dc.creatorSridhar Radhakrishnnan
dc.creatorMatthew Ricci
dc.creatorAndré Gustavo Oliveira
dc.creatorRafael Machado Rezende
dc.creatorGustavo Batista Menezes
dc.date.accessioned2023-05-25T20:03:31Z
dc.date.accessioned2025-09-08T22:52:46Z
dc.date.available2023-05-25T20:03:31Z
dc.date.issued2020
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1016/j.jhepr.2020.100117
dc.identifier.issn2589-5559
dc.identifier.urihttps://hdl.handle.net/1843/53958
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofJHEP Reports
dc.rightsAcesso Aberto
dc.subjectHepatopatia gordurosa não alcoólica
dc.subjectFígado
dc.subjectSistema Imunitário
dc.subjectDieta
dc.subjectMetabolismo
dc.subjectImunidade
dc.subject.otherNAFLD
dc.subject.otherLiver
dc.subject.otherSteatosis
dc.subject.otherImmune system
dc.subject.otherDiet
dc.subject.otherMetabolism
dc.subject.otherIn vivo imaging
dc.subject.otherImmunity
dc.titleImaging and immunometabolic phenotyping uncover changes in the hepatic immune response in the early phases of NAFLD
dc.title.alternativeA imagem e a fenotipagem imunometabólica revelam alterações na resposta imune hepática nas fases iniciais da NAFLD
dc.typeArtigo de periódico
local.citation.issue4
local.citation.volume2
local.description.resumoBackground & Aims: The precise determination of non-alcoholic fatty liver disease (NAFLD) onset is challenging. Thus, the initial hepatic responses to fat accumulation, which may be fundamental to our understanding of NAFLD evolution and clinical outcomes, are largely unknown. Herein, we chronologically mapped the immunologic and metabolic changes in the liver during the early stages of fatty liver disease in mice and compared this with human NAFLD samples. Methods: Liver biopsies from patients with NAFLD (NAFLD activity score [NAS] 2–3) were collected for gene expression profiling. Mice received a high-fat diet for short periods to mimic initial steatosis and the hepatic immune response was investigated using a combination of confocal intravital imaging, gene expression, cell isolation, flow cytometry and bone marrow transplantation assays. Results: We observed major immunologic changes in patients with NAS 2–3 and in mice in the initial stages of NAFLD. In mice, these changes significantly increased mortality rates upon drug-induced liver injury, as well as predisposing mice to bacterial infections. Moreover, deletion of Toll-like receptor 4 in liver cells dampened tolerogenesis, particularly in Kupffer cells, in the initial stages of dietary insult. Conclusion: The hepatic immune system acts as a sentinel for early and minor changes in hepatic lipid content, mounting a biphasic response upon dietary insult. Priming of liver immune cells by gut-derived Toll-like receptor 4 ligands plays an important role in liver tolerance in initial phases, but continuous exposure to insults may lead to damage and reduced ability to control infections.
local.identifier.orcidhttps://orcid.org/0000-0002-3137-991X
local.identifier.orcidhttps://orcid.org/0000-0003-4600-7593
local.identifier.orcidhttps://orcid.org/0000-0002-4926-0618
local.identifier.orcidhttps://orcid.org/0000-0002-9163-6279
local.identifier.orcidhttps://orcid.org/0000-0002-0184-6433
local.identifier.orcidhttps://orcid.org/0000-0003-4779-8972
local.identifier.orcidhttps://orcid.org/0000-0003-4779-8972
local.identifier.orcidhttps://orcid.org/0000-0001-8730-7336
local.identifier.orcidhttps://orcid.org/0000-0001-7909-6970
local.identifier.orcidhttps://orcid.org/0000-0001-5157-159X
local.identifier.orcidhttps://orcid.org/0000-0001-7724-890X
local.identifier.orcidhttps://orcid.org/0000-0003-2256-8652
local.identifier.orcidhttps://orcid.org/0000-0001-8307-0810
local.identifier.orcidhttps://orcid.org/0000-0003-3998-8012
local.publisher.countryBrasil
local.publisher.departmentENF - DEPARTAMENTO DE NUTRIÇÃO
local.publisher.departmentICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICA
local.publisher.departmentICB - DEPARTAMENTO DE MORFOLOGIA
local.publisher.departmentMED - DEPARTAMENTO DE CIRURGIA
local.publisher.departmentMED - DEPARTAMENTO DE CLÍNICA MÉDICA
local.publisher.initialsUFMG
local.url.externahttps://www.sciencedirect.com/science/article/pii/S2589555920300513?via%3Dihub

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