| Author | Nakagaki, Brenda Naemi Lanza | |
| Author | Bicalho, Kassiana Mafra | |
| Author | Carvalho, Érika de | |
| Author | Lopes, Mateus Eustáquio | |
| Author | Gontijo, Raquel Carvalho | |
| Author | Oliveira, Hortência Maciel de Castro | |
| Author | Silva, Gabriel Henrique Campolina | |
| Author | Miranda, Camila Dutra Moreira de | |
| Author | Antunes, Maísa Mota | |
| Author | Silva, Ana Carolina Carvalho | |
| Author | Diniz, Ariane Barros | |
| Author | Alvarenga, Débora Moreira | |
| Author | Lopes, Maria Alice Freitas | |
| Author | Lacerda, Viviane Aparecida de Souza | |
| Author | Mattos, Matheus Silvério | |
| Author | Araújo, Alan Moreira | |
| Author | Vidigal, Paula Vieira Teixeira | |
| Author | Lima, Cristiano Xavier | |
| Author | Mahecha, Germán Arturo Bohórquez | |
| Author | Madeira, Mila Fernandes Moreira | |
| Author | Fernandes, Gabriel Rocha | |
| Author | Nogueira, Raquel Ferraz | |
| Author | Moreira, Thais Garcias | |
| Author | David, Bruna Araújo | |
| Author | Rezende, Rafael Machado | |
| Author | Menezes, Gustavo Batista de | |
| Access date | 2022-08-19T12:02:24Z | |
| Available date | 2022-08-19T12:02:24Z | |
| Document date | 2018 | |
| Citation | NAKAGAKI, Brenda Naemi et al. Immune and metabolic shifts during neonatal development reprogram liver identity and function. Journal of Hepatology, v. 69, n. 6, p. 1294-1307, 2018. | pt_BR |
| ISSN | 0168-8278 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/54750 | |
| Sponsorship | COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR | pt_BR |
| Language | eng | pt_BR |
| Publisher | Elsevier | pt_BR |
| Rights | restricted access | pt_BR |
| Title | Immune and metabolic shifts during neonatal development reprogram liver identity and function | pt_BR |
| Type | Article | |
| DOI | 10.1016/j.jhep.2018.08.018 | |
| Abstract | Background & aims: The liver is the main hematopoietic site in embryos, becoming a crucial organ in both immunity and metabolism in adults. However, how the liver adapts both the immune system and enzymatic profile to challenges in the postnatal period remains elusive. We aimed to identify the mechanisms underlying this adaptation.
Methods: We analyzed liver samples from mice on day 0 after birth until adulthood. Human biopsies from newborns and adults were also examined. Liver immune cells were phenotyped using mass cytometry (CyTOF) and expression of several genes belonging to immune and metabolic pathways were measured. Mortality rate, bacteremia and hepatic bacterial retention after E. coli challenge were analyzed using intravital and in vitro approaches. In a set of experiments, mice were prematurely weaned and the impact on gene expression of metabolic pathways was evaluated.
Results: Human and mouse newborns have a sharply different hepatic cellular composition and arrangement compared to adults. We also found that myeloid cells and immature B cells primarily compose the neonatal hepatic immune system. Although neonatal mice were more susceptible to infections, a rapid evolution to an efficient immune response was observed. Concomitantly, newborns displayed a reduction of several macronutrient metabolic functions and the normal expression level of enzymes belonging to lipid and carbohydrate metabolism was reached around the weaning period. Interestingly, early weaning profoundly disturbed the expression of several hepatic metabolic pathways, providing novel insights into how dietary schemes affect the metabolic maturation of the liver.
Conclusion: In newborns, the immune and metabolic profiles of the liver are dramatically different to those of the adult liver, which can be explained by the differences in the liver cell repertoire and phenotype. Also, dietary and antigen cues may be crucial to guide liver development during the postnatal phase.
Lay summary: Newborns face major challenges in the extra-uterine life. In fact, organs need to modify their cellular composition and gene expression profile in order to adapt to changes in both microbiota and diet throughout life. The liver is interposed between the gastrointestinal system and the systemic circulation, being the destination of all macronutrients and microbial products from the gut. Therefore, it is expected that delicately balanced mechanisms govern the transformation of a neonatal liver to a key organ in adults. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Anatomia Patológica e Medicina Legal. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Cirurgia. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Microbiologia. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil. | pt_BR |
| Affilliation | Beckman Coulter. São Paulo, SP, Brazil. | pt_BR |
| Affilliation | Ann Romney Center for Neurologic Diseases. Brigham and Women's Hospital. Harvard Medical School. Boston, MA, USA. | pt_BR |
| Affilliation | University of Calgary. Albert, Canada. | pt_BR |
| Affilliation | Ann Romney Center for Neurologic Diseases. Brigham and Women's Hospital. Harvard Medical School. Boston, MA, USA. | pt_BR |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Centro de Biologia Gastrointestinal. Belo Horizonte, MG, Brazil. | pt_BR |
| Subject | Diet | pt_BR |
| Subject | Early weaning | pt_BR |
| Subject | Immune system | pt_BR |
| Subject | Immunity | pt_BR |
| Subject | In vivo imaging | pt_BR |
| Subject | Metabolism | pt_BR |
| Subject | Newborn | pt_BR |
