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
Processing time: 117 Days and 20.5 Hours
Abstract
BACKGROUND

Excessive saturated fat intake compromises the integrity of the intestinal mucosa, leading to low-grade inflammation, impaired mucosal integrity, and increased intestinal permeability, resulting in the migration of lipopolysaccharide (LPS) to other tissues.

AIM

To evaluate the chronic effects (at 10 and 16 wk) of a high-fat diet (HFD) (with 50% energy as fat) on the phylogenetic gut microbiota distribution and intestinal barrier structure and protection in C57BL/6 mice.

METHODS

Forty adult male mice were divided into four nutritional groups, where the letters refer to the type of diet (control and HFD or HF) and the numbers refer to the period (in weeks) of diet administration: Control diet for 10 wk, HFD for 10 wk, control diet for 16 wk, and HFD for 16 wk. After sacrifice, biochemical, molecular, and stereological analyses were performed.

RESULTS

The HF groups were overweight, had gut dysbiosis, had a progressive decrease in occludin immunostaining, and had increased LPS concentrations. Dietary progression reduced the number of goblet cells per large intestine area and Mucin2 expression in the HF16 group, consistent with a completely disarranged intestinal ultrastructure after 16 wk of HFD intake.

CONCLUSION

Chronic HFD intake causes overweight, gut dysbiosis, and morphological and functional alterations of the intestinal barrier after 10 or 16 wk. Time-dependent reductions in goblet cell numerical density and mucus production have emerged as targets for countering obesity-driven intestinal damage.

Keywords: High-fat diet; Intestine; Ultrastructure; Goblet cells; Gut microbiota

Core Tip: There is great interest in the scientific community in the impact of unhealthy eating habits, such as excess saturated fatty acid intake, on the gut microbiota composition and metabolic disease onset. Here, we evaluated the progressive changes in the intestinal structural barrier and gut microbiota composition in mice fed a high-fat diet (HFD) for 10 or 16 wk. HFD administration resulted in gut dysbiosis, compensatory enhancement of goblet cell numerical density, and increased Mucin2 expression after 10 wk. Continuous feeding reduced the goblet cell number and the expression of Mucin2 and occludin, consistent with the impaired tight junction ultrastructure in the chronically obese HFD-fed mice after 16 wk.