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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2022; 28(17): 1814-1829
Published online May 7, 2022. doi: 10.3748/wjg.v28.i17.1814
Published online May 7, 2022. doi: 10.3748/wjg.v28.i17.1814
Peroxisome proliferator-activated receptor-alpha activation and dipeptidyl peptidase-4 inhibition target dysbiosis to treat fatty liver in obese mice
Flavia Maria Silva-Veiga, Carolline Santos Miranda, Isabela Macedo Lopes Vasques-Monteiro, Henrique Souza-Tavares, Fabiane Ferreira Martins, Vanessa Souza-Mello, Department of Anatomy, Institute of Biology, State University of Rio de Janeiro, Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Rio de Janeiro 20551-030, Brazil
Julio Beltrame Daleprane, Department of Clinical and Toxicology Analysis, State University of Rio de Janeiro, Nutrition Institute, State University of Rio de Janeiro, Nutrition Institute, University of Sao Paulo, Rio de Janeiro 20551-030, Brazil
Author contributions: Silva-Veiga FM, Martins FF, Daleprane JB, and Souza-Mello V designed and coordinated the study; Silva-Veiga FM, Miranda CS, Vasques-Monteiro IML, Souza-Tavares H, Martins FF, Daleprane JB, and Souza-Mello V performed the experiments, acquired and analyzed data; Silva-Veiga FM, Miranda CS, Vasques-Monteiro IML, Martins FF, Daleprane JB, and Souza-Mello V interpreted the data; Silva-Veiga FM and Souza-Mello V wrote the manuscript; all authors approved the final version of the article.
Supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil , No. CAPES–Finance Code 001 ; Fundação Carlos Chagas Filho de Amparo à Pesquisa do Rio de Janeiro (FAPERJ) to Souza-Mello V , No. E-26/202.657/2018 and No. E-26/010.002136/2019 ; The corresponding author is supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) , No. 303785/2020-9 .
Institutional review board statement: The study was reviewed and approved by the CEUA of State University of Rio de Janeiro Institutional Review Board, No. 041/2018.
Conflict-of-interest statement: The authors have no conflict of interest to declare.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at souzamello.uerj@gmail.com.
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, Institute of Biology, State University of Rio de Janeiro, Laboratory of Morphometry, Metabolism and Cardiovascular Diseases, Blvd. 28 de Setembro 87, Fundos, Vila Isabel, Rio de Janeiro 20551-030, Brazil. souzamello.uerj@gmail.com
Received: December 30, 2021
Peer-review started: December 30, 2021
First decision: January 27, 2022
Revised: February 4, 2022
Accepted: March 26, 2022
Article in press: March 26, 2022
Published online: May 7, 2022
Processing time: 119 Days and 13.8 Hours
Peer-review started: December 30, 2021
First decision: January 27, 2022
Revised: February 4, 2022
Accepted: March 26, 2022
Article in press: March 26, 2022
Published online: May 7, 2022
Processing time: 119 Days and 13.8 Hours
Core Tip
Core Tip: Chronic high-fat diet (HF) intake alters the phylogenetic microbiota composition, sending harmful proinflammatory signals to the liver that elicit nonalcoholic fatty liver disease in mice. Here, we treated HF diet-induced obese mice with a peroxisome proliferator-activated receptor-alpha agonist (WY14643), a dipeptidyl-peptidase-4 inhibitor (linagliptin), or their combination, focusing on gut–liver axis modulation. The treatments rescued gut dysbiosis and endotoxemia due to increased tight junction gene expression, mucin production, and numerical density of goblet cells in the intestinal crypts. Treated mice benefited from downregulated Tlr4, Cd206, and Nlrp3, alleviating fatty liver through anti-inflammatory signals such as increased IL-10 and IL-13.