Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Aug 27, 2019; 11(8): 619-637
Published online Aug 27, 2019. doi: 10.4254/wjh.v11.i8.619
Prolonged high-fat-diet feeding promotes non-alcoholic fatty liver disease and alters gut microbiota in mice
Kandy T Velázquez, Reilly T Enos, Jackie E Bader, Alexander T Sougiannis, Meredith S Carson, Ioulia Chatzistamou, James A Carson, Prakash S Nagarkatti, Mitzi Nagarkatti, E Angela Murphy
Kandy T Velázquez, Reilly T Enos, Jackie E Bader, Alexander T Sougiannis, Meredith S Carson, Ioulia Chatzistamou, James A Carson, Prakash S Nagarkatti, Mitzi Nagarkatti, E Angela Murphy, Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
James A Carson, College of Health Professions, University of Tennessee Health Sciences Center, Memphis, TN 38163, United States
Author contributions: Velázquez KT performed the majority of experiments and analyzed the data; Chatzistamou I performed histopathological analysis; Velázquez KT performed staining; Velázquez KT, Enos RT, Carson MS, and Sougiannis AT performed molecular investigations; Velázquez KT, Bader JE, Nagarkatti PS, Nagarkatti M and Murphy EA designed and coordinated the microbiome research; Velázquez KT, Enos RT, Carson JA and Murphy EA designed and coordinated the obesity and non-alcoholic fatty liver disease research; Velázquez KT, Enos RT, and Murphy EA wrote the paper; all authors were involved in editing the manuscript.
Supported by National Institute of Health, No. NCI-3R01CA121249-08S1, NCCIH-K99AT009206 and No. NCI-1R21CA191966.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee at the University of South Carolina.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: Data from this manuscript will be available upon request.
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 which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: E Angela Murphy, PhD, Associate Professor, Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, 6439 Garners Ferry Rd, Columbia, SC 29209, United States. angela.murphy@uscmed.sc.edu
Telephone: +1-803-2163414 Fax: +1-803-2163414
Received: March 7, 2019
Peer-review started: March 11, 2019
First decision: April 11, 2019
Revised: July 5, 2019
Accepted: July 16, 2019
Article in press: July 17, 2019
Published online: August 27, 2019
ARTICLE HIGHLIGHTS
Research background

Animal models that can exhibit characteristics seen in non-alcoholic fatty liver disease (NAFLD) have the potential to drive the discovery of new drugs to treat this disease.

Research motivation

Most animal models used to investigate NAFLD misrepresent typical characteristics seen in human patients with NAFLD. Therefore, any successful treatments documented in these animal models may not be clinically translatable.

Research objectives

To evaluate if mice consuming a high calorie diet for a prolonged time can mimic clinical characteristics of NAFLD.

Research methods

Male mice (10 wk old) were assigned to the following groups: Young- low-fat diet (LFD) (n = 20; low calorie diet for), Old-LFD (n = 15; low calorie diet), and Old-HFD (n = 18; high calorie diet). Mice in the LFD consumed a diet rich in carbohydrates, meanwhile the HFD was abundant in fat content. Liver, colon, adipose tissue, and feces were collected at 16 wk of age in Young-LFD mice and at 90 wk of age in Old-LFD and Old-HFD to evaluate microscopic features, glucose metabolism, inflammation, endoplasmic reticulum (ER) stress, and microbiome profile seen in NAFLD.

Research results

Old-HFD mice showed increased body weight, blood glucose, plasma insulin, HOMA index, steatosis, hepatocellular ballooning, inflammation, fibrosis, NAFLD activity score, ER stress markers (CHOP and p-Jnk), and abundance of Firmicutes, Adlercreutzia, Turicibacter, Coprococcus, Dorea, and Ruminococcus.

Research conclusions

Mice fed a high calorie diet for 80-wk (Old-HFD) mimicked microscopic characteristic and microbial events that have been previously observed in NAFLD patients.

Research perspectives

It is important to critically select animal models to study any disease including NAFLD. Future research dedicated to investigation of new treatments for NAFLD should consider prolonged-HFD feedings as their animal model.