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Partial validation of a six-month high-fat diet and fructose-glucose drink combination as a mouse model of nonalcoholic fatty liver disease.

Endocrine
August 1, 2024
Evangelia S Makri et al. (11 authors)
Journal ArticleValidation StudyAnimal Study
Study Details

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.

Extracted Claims (15)
InterventionDirectionEndpointPopulationDosageImpactClaim #
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
Abstract

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.

Medical Subject Headings (MeSH)
AnimalsNon-alcoholic Fatty Liver DiseaseMaleFemaleDisease Models, AnimalDiet, High-FatFructoseMiceMice, Inbred C57BLLiverGlucoseAlanine TransaminaseAspartate AminotransferasesTriglyceridesBlood GlucoseBeveragesCholesterol
Study Links
Quality Scores
SafetyNot Assessed
Efficacy60/10
Quality75/10
Citation Metrics
Total Citations3
Citations/Year3.0
Research Impact Scores
APT Score0.05
Weight Score2.00
Normalized Score0.59
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