Basic Study
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World J Methodol. Mar 20, 2024; 14(1): 89723
Published online Mar 20, 2024. doi: 10.5662/wjm.v14.i1.89723
Time-dependent impact of a high-fat diet on the intestinal barrier of male mice
Carolline Santos Miranda, Daiana Araujo Santana-Oliveira, Isabela Lopes Vasques-Monteiro, Nathan Soares Dantas-Miranda, Jade Sancha de Oliveira Glauser, Flavia Maria Silva-Veiga, Vanessa Souza-Mello
Carolline Santos Miranda, Daiana Araujo Santana-Oliveira, Isabela Lopes Vasques-Monteiro, Nathan Soares Dantas-Miranda, Jade Sancha de Oliveira Glauser, Flavia Maria Silva-Veiga, Vanessa Souza-Mello, Department of Anatomy, Rio de Janeiro State University, Rio de Janeiro 20551030, Brazil
Author contributions: Miranda CS, Santana-Oliveira DA, Vasques-Monteiro IL, Silva-Veiga FM, and Souza-Mello V designed and coordinated the study, and interpreted the data; Miranda CS, Santana-Oliveira DA, Vasques-Monteiro IL, Dantas-Miranda NS, and Glauser JSO performed the experiments, and acquired and analyzed the data; Miranda CS, Santana-Oliveira DA, Vasques-Monteiro IL, and Silva-Veiga FM wrote the manuscript; and all authors approved the final version of the article.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (the local Ethics Committee, Institute of Biology, State University of Rio de Janeiro, CEUA Nº 017/2021).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Vanessa Souza-Mello, PhD, Associate Professor, Department of Anatomy, Rio de Janeiro State University, Blvd. 28 de setembro 87, fundos, Rio de Janeiro 20551030, Brazil. souzamello.uerj@gmail.com
Received: November 10, 2023
Peer-review started: November 10, 2023
First decision: December 17, 2023
Revised: December 26, 2023
Accepted: February 18, 2024
Article in press: February 18, 2024
Published online: March 20, 2024
ARTICLE HIGHLIGHTS
Research background

There is great interest in the scientific community in the role of gut dysbiosis in obesity and metabolic impairments. However, there is little evidence in the literature on the progressive impact of a high-fat diet (HFD) on mouse intestinal barrier structure and microbiota composition.

Research motivation

Recently, different dietary models and durations of diet administration have yielded controversial results regarding the QA (goblet cells), mucus layer, and microbiota composition in mice with diet-induced obesity. Considering the importance of understanding the progressive changes in intestinal structure and microbiota composition that occur during obesity onset, we examined these changes after 10 or 16 wk of HFD feeding to establish tools to characterize obesity-related intestinal impairments.

Research objectives

We further studied the chronic effects (at 10 and 16 wk) of an HFD (with 50% energy as fat) on the phylogenetic gut microbiota distribution and intestinal barrier structure and protection in C57BL/6 mice. The study considered the mouse model, diet composition, and duration of intervention that were most prevalent in the literature.

Research methods

Mice were fed ad libitum, and food intake and body mass gain were monitored during the experiment. Intestinal samples were subjected to light and electron microscopy, and plasma lipopolysaccharide concentrations were determined through ELISA. After 16S rRNA gene amplification by qPCR was performed on the frozen cecal feces to determine the phylogenetic microbiota distribution, the ileum samples were subjected to qPCR analysis for Occludin expression.

Research results

Our results confirmed that body mass increased gradually with HFD feeding without altering food intake. Dysbiosis in the HFD model involved an increase in Firmicutes and a decrease in Bacteroidetes concomitant with an increase in plasma lipopolysaccharide concentrations, so-called endotoxemia. The original findings were compensatory goblet cell hyperplasia and increased Mucin2 expression in the tenth week, followed by a drastic reduction in both parameters after 16 wk of HFD feeding. These structural alterations were consistent with the progressive damage to the intestinal ultrastructure in obese mice.

Research conclusions

Chronic HFD intake causes gut dysbiosis and endotoxemia, with time-dependent overweight, and morphological and functional alterations of the intestinal barrier after 10 or 16 wk. We identified QA (goblet cells) and mucin expression as viable tools to address the progressive damage caused by obesity in the intestine.

Research perspectives

The evaluation of QA (goblet cells), functionality, and ultrastructure has led to the identification of potential targets for addressing the impact of excessive saturated fatty acid intake on the intestine.