Partial validation of a six-month high-fat diet and fructose-glucose drink combination as a mouse model of nonalcoholic fatty liver disease.
Study Goal
The researchers aimed to validate a fast food diet (FFD) mouse model for studying nonalcoholic fatty liver disease (NAFLD) and its resemblance to human disease.
Results Summary
FFD mice showed increased weight, liver-to-body weight ratio, steatosis, hepatocellular ballooning, and NAFLD activity score (NAS) compared to chow diet mice, but no significant differences in lobular inflammation or fibrosis. The model partially validated NAFLD features over a 6-month period.
Population
Male and female C57BL/6J mice aged 8-9 weeks.
Effective Dosage
Not specified (fast food diet composition not detailed).
Duration
25 weeks.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
fast food diet (FFD) | increase | weight | C57BL/6 J mice | p = 0.049 | gained more weight | #1 |
fast food diet (FFD) | increase | liver-to-body weight ratio | C57BL/6 J mice | p < 0.001 | presented a higher liver-to-body weight ratio | #2 |
fast food diet (FFD) | increase | steatosis | C57BL/6 J mice | - | presented with greater steatosis | #3 |
fast food diet (FFD) | increase | hepatocellular ballooning | C57BL/6 J mice | - | presented with greater hepatocellular ballooning | #4 |
fast food diet (FFD) | increase | NAFLD activity score (NAS) | C57BL/6 J mice | - | presented with greater NAFLD activity score (NAS) | #5 |
fast food diet (FFD) | no change | lobular inflammation | C57BL/6 J mice | - | lobular inflammation was not significantly different | #6 |
fast food diet (FFD) | no change | fibrosis | C57BL/6 J mice | - | fibrosis was not significantly different | #7 |
fast food diet (FFD) | increase | NAFLD activity score (NAS) | male mice | - | NAS was different | #8 |
fast food diet (FFD) | increase | NAFLD activity score (NAS) | female mice | - | NAS was different | #9 |
fast food diet (FFD) | increase | weight | C57BL/6 J mice | - | group by time interaction was significant for weight | #10 |
fast food diet (FFD) | increase | alanine aminotransferase (ALT) | C57BL/6 J mice | - | group by time interaction was significant for ALT | #11 |
fast food diet (FFD) | increase | total cholesterol | C57BL/6 J mice | - | group by time interaction was significant for cholesterol | #12 |
fast food diet (FFD) | no change | glucose | C57BL/6 J mice | - | group by time interaction was not significant for glucose | #13 |
fast food diet (FFD) | no change | aspartate aminotransferase (AST) | C57BL/6 J mice | - | group by time interaction was not significant for AST | #14 |
fast food diet (FFD) | no change | triglycerides (TGs) | C57BL/6 J mice | - | group by time interaction was not significant for TGs | #15 |
PURPOSE: The need to investigate the pathogenesis and treatment of nonalcoholic fatty liver disease (NAFLD) has led to the development of multiple mouse models. The aim of this study was to validate a fast food diet (FFD) mouse model that is introduced as being close to the human disease. METHODS: Eight to nine weeks old male and female C57BL/6 J mice were randomly allocated to a FFD group or to a chow diet (CD) group. Every four weeks, mice were weighed, and blood samples were collected for the measurement of glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TGs) and total cholesterol. After 25 weeks, mice were sacrificed, and liver tissue was histologically evaluated. RESULTS: FFD mice gained more weight (p = 0.049) and presented a higher liver-to-body weight ratio (p < 0.001) compared to CD mice. FFD group presented with greater steatosis, hepatocellular ballooning and NAFLD activity score (NAS), whereas lobular inflammation and fibrosis were not significantly different compared to CD. When stratified by sex, NAS was different between FFD and CD groups in both male and female mice. Group by time interaction was significant for weight, ALT and cholesterol, but not for glucose, AST and TGs. CONCLUSION: FFD mice presented with morphologic and biochemical features of NAFLD and with greater hepatic steatosis, hepatocellular ballooning and NAS, but not lobular inflammation and fibrosis, compared to CD mice. These results only partly validate the FFD mouse model for NAFLD, at least for a 6-month feeding period.