Published online Aug 27, 2019. doi: 10.4254/wjh.v11.i8.619
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
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.
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.
To evaluate if mice consuming a high calorie diet for a prolonged time can mimic clinical characteristics of NAFLD.
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.
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.
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.
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.