Key result
Western diet-fed ApoE knockout male mice developed fundamental parameters of NASH, including hepatic steatosis, fibrosis, inflammation, and metabolic syndrome, after 7 weeks.
Why the study?
Rodent models of NASH currently lack significant aspects of the full disease spectrum, prompting the need for a fast model exhibiting all characteristic NASH features.
Does a Western diet induce characteristic features of NASH in ApoE KO male mice?
Does a Western diet induce characteristic features of NASH in ApoE KO male mice?
ApoE KO male mice fed a Western diet for 7 weeks serve as a fast and comprehensive experimental model for NASH research, exhibiting key features of steatosis, fibrosis, and inflammation.
May advance preclinical NASH research with a comprehensive rodent model; leaves open human translation.
One of the consequences of the Western lifestyle and high-fat diet is non-alcoholic fatty liver disease (NAFLD) and its aggressive form, non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma (HCC) and is rapidly becoming the leading cause of end-stage liver disease or liver transplantation. Currently, rodent NASH models lack significant aspects of the full NASH spectrum, representing a major problem for NASH research. Therefore, this work aimed to characterize a fast rodent model with all characteristic features of NASH. Eight-week-old male ApoE KO mice were fed with Western diet (WD), high fatty diet (HFD) or normal chow (Chow) for 7 weeks. Whole-body fat was increased by ~2 times in WD mice and HFD mice and was associated with increased glucose intolerance, hepatic triglycerides, and plasma ALT and plasma AST compared with Chow mice. WD mice also showed increased galectin-3 expression compared with Chow or HFD mice and increased plasma cholesterol compared with Chow mice. WD and HFD displayed increased hepatic fibrosis and increased F4/80 expression. WD mice also displayed increased levels of plasma MCP-1. Hepatic inflammatory markers were evaluated, and WD mice showed increased levels of TNF-α, MCP-1, IL-6 and IFN-γ. Taken together, these data demonstrated that the ApoE KO mouse fed with WD is a great model for NASH research, once it presents the fundamental parameters of the disease, including hepatic steatosis, fibrosis, inflammation, and metabolic syndrome.
No takes yet. Share an insight, caveat, or question.
Camargo et al. (2022) studied Non-alcoholic steatohepatitis (NASH). Western diet (WD) vs. High fatty diet (HFD) or normal chow (Chow) was evaluated on Characterization of NASH features (hepatic steatosis, fibrosis, inflammation, metabolic syndrome). Western diet-fed ApoE knockout male mice developed fundamental parameters of NASH, including hepatic steatosis, fibrosis, inflammation, and metabolic syndrome, after 7 weeks.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: