| Full text | |
| Author(s): |
Romualdo, Guilherme R.
;
Valente, Leticia Cardoso
;
Sprocatti, Ana Carolina
;
Bacil, Gabriel Prata
;
de Souza, Isadora Penedo
;
Rodrigues, Josias
;
Rodrigues, Maria Aparecida Marchesan
;
Vinken, Mathieu
;
Cogliati, Bruno
;
Barbisan, Luis Fernando
Total Authors: 10
|
| Document type: | Journal article |
| Source: | NUTRITION; v. 103-104, p. 12-pg., 2022-10-03. |
| Abstract | |
Objectives: Non-alcoholic fatty liver disease (NAFLD) has a growing epidemiologic and economic burden. It is associated with Western diet (WD) patterns, and its pathogenesis involves metabolic disorders (obesity, dys-lipidemia, hyperglycemia, and diabetes) and gut dysbiosis, features that are usually neglected or not repro-duced by most animal models. Thus, we established a 6-mo WD-induced NAFLD mouse model associated with metabolic disorder, investigating its main features at the gut microbiome-liver-adipose tissue axis, also evaluating the correlations of gut dysbiosis to the other disease outcomes.Methods: Male C57 BL6 mice received a high-fat (30% lard and 0.2% cholesterol,-57% calories) and sucrose -rich (20%) chow, and a high-sugar solution (23.1 and 18.9 g/L of D-fructose and D-glucose) for 6 mo.Results: The model featured high serum cholesterol levels, glucose intolerance, and hyperinsulinemia. WD intervention resulted in extensive macro/microvesicular liver steatosis and pericellular fibrosis-resembling human disease-accompanied by hepatic stellate cell activation and CD68+ macrophage infiltration, increased protein levels of proinflammatory p65-nuclear factor-kB, interleukin-6 and tumor necrosis factor -a, with decreased antioxidant regulator Nrf2. Mice showed clear obesity with adipocyte hypertrophy, and CD68+macrophage/mast cell infiltration in adipose tissue while a reduction in number of goblet cells was also observed in the small intestine. Moreover, the pyrosequencing of the 16 S ribosomal RNA of gut cecal content showed decreased bacterial diversity, enriched Firmicutes and Proteobacteria, decreased Bacteroi-detes and Fusobacteria, and increased ratio of Firmicutes to Bacteroidetes. Bacteroidetes and Bacteroides had the highest number of significant correlations with liver-adipose tissue axis outcomes. In silico analysis of gut microbiome in NAFLD obese patients revealed a depletion in Bacteroides, which also correlated to disease outcomes. Conclusion: This mice model gathered suitable phenotypical alterations in gut-liver-adipose tissue axis that resembled NAFLD associated with metabolic disorders in humans and may be considered for preclinical investigation.(c) 2022 Elsevier Inc. All rights reserved. (AU) | |
| FAPESP's process: | 21/07954-6 - Glyphosate implications on Metabolic-associated Fatty Liver Desease in mice: role of NFR2, p65, SREBP1 transcription factors |
| Grantee: | Ana Carolina Sprocatti dos Santos |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| FAPESP's process: | 20/00377-0 - Effects of glyphosate and 2,4-D exposure on non-alcoholic steatohepatitis development in mice: Insights on contemporary exposition patterns? |
| Grantee: | Guilherme Ribeiro Romualdo |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 20/01078-7 - Glyphosate and 2,4-D implications on Non-alcoholic fatty liver disease in vivo: transcriptome and microbiome analysis |
| Grantee: | Luís Fernando Barbisan |
| Support Opportunities: | Regular Research Grants |